Sankar Basu

Asutosh College

Disrupted genes linked to mental disorders sometimes exhibit characteristics of Intrinsically Disordered Proteins (IDPs). However, few studies have comprehensively explored the functional associations between protein disorder properties and different psychiatric disorders. In this study, we collected disrupted proteins for seven mental diseases (MD...

Microscopic evolution at the functional biomolecular level is an ongoing process. Leveraging functional and high-throughput assays, along with computational data mining, has led to a remarkable expansion of our understanding of multifunctional protein (and gene) families over the past few decades. Various molecular and intermolecular mechanisms are...

The combined effect of shape and electrostatic complementarities (Sc, EC) at the interface of the interacting protein partners (PPI) serves as the physical basis for such associations and is a strong determinant of their binding energetics. EnCPdock (https://www.scinetmol.in/EnCPdock/) presents a comprehensive web platform for the direct conjoint c...

Intrinsically Disordered Proteins (IDPs) play crucial roles in signal transduction, cell differentiation, and transcriptional regulation. Many disrupted genes associated with mental disorders are identified as IDPs, and emerging evidence suggests the functional role of IDPs in neuropsychiatric disorders. However, few studies comprehensively explore...

The combined efect of shape and electrostatic complementarities (Sc, EC) at the interface of the interacting protein partners (PPI) serves as the physical basis for such associations and is a strong detterminant of their binding energetics. EnCPdock (https://www.scinetmol.in/EnCPdock/) presents a comprehensive web-platform for the direct conjoint c...

Context: Protein-protein interaction (PPI) is a key component linked to virtually all cellular processes. Be it an enzyme catalysis ('classic type functions' of proteins) or a signal transduction ('non-classic'), proteins generally function involving stable or quasi-stable multi-protein associations. The physical basis for such associations is inh...

Context Protein-protein interaction (PPI) is a key component linked to virtually all cellular processes. Be it an enzyme catalysis (‘classic type functions ’ of proteins) or a signal transduction (‘ non-classic’ ), proteins generally function involving stable or quasi-stable multi-protein associations. The physical basis for such associations is in...

Recording of the talk is available at the following link (Please copy-paste in a browser address bar): https://www.youtube.com/watch?v=3PhpQ_sHLIo

Recording of the talk is available at the following link (copy-paste in a browser address bar): https://www.youtube.com/watch?v=9diSiaJvGg8

The COVID-19 origin debate has greatly been influenced by genome comparison studies of late, revealing the emergence of the Furin-like cleavage site at the S1/S2 junction of the SARS-CoV-2 Spike (FLCSSpike) containing its 681PRRAR685 motif, absent in other related respiratory viruses. Being the rate-limiting (i.e., the slowest) step, the host Furin...

According to the ‘jigsaw puzzle’ model of protein folding, the isomorphism between sequence and structure is substantially determined by the specific geometry of side‐chains interactions, within the protein interior. In this work, we have attempted to predict the hydrophobic core of cyclophilin (LdCyp) from Leishmania donovani, utilizing a surface...

The COVID-19 origin debate has greatly been influenced by Genome comparison studies of late, revealing the seemingly sudden emergence of the Furin-Like Cleavage Site at the S1/S2 junction of the SARS-CoV-2 Spike (FLCS_Spike) containing its 681_PRRAR_685 motif, absent in other related respiratory viruses. Being the rate-limiting (i.e., the slowest)...

Understanding the role of stability strengths and weaknesses in proteins is a key objective for rationalizing their dynamical and functional properties such as conformational changes, catalytic activity, and protein-protein and protein-ligand interactions. We present BRANEart, a new, fast and accurate method to evaluate the per-residue contribution...

As is well known, the emergence of SARS-CoV-2 ever since late 2019 [...]

Understanding the role of stability strengths and weaknesses in proteins is a key objective for rationalizing their dynamical and functional properties such as conformational changes, catalytic activity, and protein-protein and protein-ligand interactions. We present BRANEart, a new, fast and accurate method to evaluate the per-residue contribution...

COVID-19 is characterized by an unprecedented abrupt increase in the viral transmission rate (SARS-CoV-2) relative to its pandemic evolutionary ancestor, SARS-CoV (2003). The complex molecular cascade of events related to the viral pathogenicity is triggered by the Spike protein upon interacting with the ACE2 receptor on human lung cells through it...

COVID-19 is characterized by an unprecedented abrupt increase in the viral transmission rate (SARS-CoV-2) relative to its pandemic evolutionary ancestor, SARS-CoV (2003). The complex molecular cascade of events related to the viral pathogenicity is triggered by the Spike protein upon interacting with the ACE2 receptor on human lung cells through it...

COVID-19 is characterized by an unprecedented abrupt increase in transmission rate relative to its endemic evolutionary ancestor, SARS-CoV (2003). The complex molecular cascade of events related to the viral pathogenicity is triggered by the Spike protein upon interacting with the ACE2 receptor on human lung cells through its receptor binding domai...

Intrinsically disordered proteins (IDP) serve as one of the key components in the global proteome. In contrast to globular proteins, they harbor an enormous amount of physical flexibility enforcing them to be retained in conformational ensembles rather than stable folds. Previous studies in an aligned direction have revealed the importance of trans...

Intrinsically disordered proteins (IDP) serve as one of the key components in the proteome. In contrast to the dominant class of cytosolic globular proteins, they harbor an enormous amount of physical flexibility or structural plasticity enforcing them to be retained in conformational ensembles rather than well defined stable folds. Previous studie...

Graph coloring is a manifestation of graph partitioning, wherein a graph is partitioned based on the adjacency of its elements. The fact that there is no general efficient solution to this problem that may work unequivocally for all graphs opens up the realistic scope for combinatorial optimization algorithms to be invoked. The algorithmic complexi...

Graph Coloring Problem is a 200-years old HARD problem in Combinatorics, Mathematics, also enlisted in Karp's famous list of 21 NP-complete problems. The paper can be found here or I can email a pdf on request. https://link.springer.com/article/10.1007%2Fs00500-019-04278-8

Transmembrane proteins play a fundamental role in a wide series of biological processes but, despite their importance, they are less studied than globular proteins, essentially because their embedding in lipid membranes hampers their experimental characterization. In this paper, we improved our understanding of their structural stability through th...

Electrostatic potential, energies, and forces affect virtually any process in molecular biology, however, computing these quantities is a difficult task due to irregularly shaped macromolecules and the presence of water. Here, we report a new edition of the popular software package DelPhi along with describing its functionalities. The new DelPhi is...

Transmembrane proteins play a fundamental role in a wide series of biological processes but, despite their importance, they are less studied than globular proteins, essentially because their embedding in lipid membranes hampers their experimental characterization. In this paper, we improved our understanding of their structural stability through th...

Structural information of biological macromolecules is crucial and necessary to deliver predictions about the effects of mutations—whether polymorphic or deleterious (i.e., disease causing), wherein, thermodynamic parameters, namely, folding and binding free energies potentially serve as effective biomarkers. It may be emphasized that the effect of...

Structural information of biological macromolecules is crucial and necessary to deliver predictions about the effects of mutations—whether polymorphic or deleterious (i.e., disease causing), wherein, thermodynamic parameters, namely, folding and binding free energies potentially serve as effective biomarkers. It may be emphasized that the effect of...

Structural information of biological macromolecules is crucial and necessary to deliver predictions about the effects of mutations—whether polymorphic or deleterious (i.e., disease causing), wherein, thermodynamic parameters, namely, folding and binding free energies potentially serve as effective biomarkers. It is to be emphasized that the effect...

Structural information of biological macromolecules is crucial and necessary to deliver predictions about the effects of mutations—whether polymorphic or deleterious (i.e., disease causing), wherein, thermodynamic parameters, namely, folding and binding free energies potentially serve as effective biomarkers. It is to be emphasized that the effect...

The DelPhiPKa is a widely used and unique approach to compute pKa's of ionizable groups that does not require molecular surface to be defined. Instead, it uses smooth Gaussian‐based dielectric function to treat computational space via Poisson‐Boltzmann equation (PBE). Here we report an expansion of DelPhiPKa functionality to enable inclusion of sal...

Nanoparticle bioreactivity critically depends upon interaction between proteins and nanomaterials (NM). The formation of the “protein corona” (PC) is the effect of such nanoprotein interactions. PC has a wide usage in pharmaceuticals, drug delivery, medicine, and industrial biotechnology. Therefore, a detailed in-vitro, in-vivo, and in-silico under...

Graph coloring is a manifestation of graph partitioning, wherein, a graph is partitioned based on the adjacency of its elements. Partitioning serves potentially as a compartmentalization for any structural problem. Vertex coloring is the heart of the problem which is to find the chromatic number of a graph. The fact that there is no general efficie...

Intrinsically Disordered Proteins (IDPs) are enriched in charged and polar residues; and, therefore, electrostatic interactions play a predominant role in their dynamics. In order to remain multi-functional and exhibit their characteristic binding promiscuity, they need to retain considerable dynamic flexibility. At the same time, they also need to...

Intrinsically Disordered Proteins (IDPs) are enriched in charged and polar residues; and, therefore, electrostatic interactions play a predominant role in their dynamics. In order to remain multi-functional and exhibit their characteristic binding promiscuity, they need to retain considerable dynamic flexibility. At the same time, they also need to...

The complementarity plot (CP) is an established validation tool for protein structures, applicable to both globular proteins (folding) as well as protein-protein complexes (binding). It computes the shape and electrostatic complementarities (Sm, Em) for amino acid side-chains buried within the protein interior or interface and plots them in a two-d...

The Complementarity plot (CP) is an established validation tool for protein structures, applicable to both, globular proteins (folding) as well as protein-protein complexes (binding). It computes the shape and electrostatic complementarities (S m , E m ) for amino acid side-chains buried within the protein interior or interface and plots them in a...

Nitric oxide (NO) acts as a signalling molecule that has direct and indirect regulatory roles in various functional processes in biology, though in plant kingdom its role is relatively unexplored. One reason for this is the fact that sensing of NO is always challenging. There are very few probes that can classify the different NO species. The prese...

There has been considerable debate about the contribution of salt bridges to the stabilization of protein folds, in spite of their participation in crucial protein functions. Salt bridges appear to contribute to the activity–stability trade-off within proteins by bringing high-entropy charged amino acids into close contacts during the course of the...

Nitric oxide (NO) acts as a signalling molecule that has direct and indirect regulatory roles in various functional processes in biology, though in plant kingdom its role is relatively unexplored. One reason for this is the fact that sensing of NO is always challenging. There are very few probes that can classify the different NO species. The prese...

The focus of the computational structural biology community has taken a dramatic shift over the past one-and-a-half decades from the classical protein structure prediction problem to the possible understanding of intrinsically disordered proteins (IDP) or proteins containing regions of disorder (IDPR). The current interest lies in the unraveling of...

The focus of the computational structural biology community has taken a dramatic shift over the past one-and-a-half decades from the classical protein structure prediction problem to the possible understanding of intrinsically disordered proteins (IDP) or proteins containing regions of disorder (IDPR). The current interest lies in the unraveling of...

There has been fare amount of debate regarding the contribution of salt-bridges in the stabilization of protein folds. However, their participation in crucial protein functions are well established. The current study analyzes their modes of association, in terms of networks, both within globular proteins and also at protein-protein interfaces. Apar...

Comprehensive analyses of structural features of non-canonical base pairs within a nucleic acid double helix are limited by the availability of a small number of three dimensional structures. Therefore, a procedure for model building of double helices containing any given nucleotide sequence and base pairing information, either canonical or non-can...

The state-of-the-art to assess the structural quality of docking models is currently based on three related yet independent quality measures: Fnat, LRMS, and iRMS as proposed and standardized by CAPRI. These quality measures quantify different aspects of the quality of a particular docking model and need to be viewed together to reveal the true qua...

Supporting Figures. Figure A. Demonstration of the Inverse Square Scaling technique. The scaling parameter, k, describes the raw score (X) at half maximal high (0.5) of the scaled score, Y. k is set to 8.5 in this example illustration which is the optimized value for LRMS. Figure B. Heat map with average F1-values for the optimization of d1 and d2...

Motivation: Protein–protein interactions are a key in virtually all biological processes. For a detailed understanding of the biological processes, the structure of the protein complex is essential. Given the current experimental techniques for structure determination, the vast majority of all protein complexes will never be solved by experimental...

Currently, considerable interest exists with regard to the dissociation of close packed ami-noacids within proteins, in the course of unfolding, which could result in either wet or dry mol-tenglobules. The progressive disjuncture of residues constituting the hydrophobic core ofcyclophilin from L. donovani (LdCyp) has been studied during the thermal...

Following our previous report of a graphical structural validation tool for single domain globular proteins namely the Complementarity Plot (SARAMA, available at http://www.saha.ac.in/biop/www/sarama.html), here we report the further development of the software (SARAMAint) for protein–protein interfaces available in the same webpage as a separate d...

The complementarity plot (CP) is based on packing and electrostatics of amino acid residues buried within globular proteins and is a sensitive indicator of the harmony or disharmony of interior residues with regard to short and long range forces sustaining the native fold. As a structure validation tool, it has already been reported to be effective...

RNA contains different secondary structural motifs like pseudo-helices, hairpin loops, internal loops, etc. in addition to anti-parallel double helices and random coils. The secondary structures are mainly stabilized by base-pairing and stacking interactions between the planar aromatic bases. The hydrogen bonding strength and geometries of base pai...

The protein folding problem remains a major unsolved problem in structural biology. In one aspect it deals with the mapping of protein primary sequences to their three dimensional folds, referred to as the second genetic code. Two factors which condition the isomorphism between sequence and fold, are (1) the pattern of hydrophobicities embedded in...

Cyclophilin from Leishmania donovani (LdCyp) is a ubiquitous peptidyl-prolyl cis-trans isomerase involved in a host of important cellular activities such as signaling, heat shock response, chaperone activity, mitochondrial pore maintenance and regulation of HIV-1 infectivity. It also acts as the prime cellular target for the auto-immune drug cyclos...

Background / Purpose: Structure validation is a crucial component not only in protein crystallography but also in model quality estimation in homology modeling, protein design and de novo structure prediction. Recent studies have emphasized on the need to improve existing validation tools with the rapid growth of protein crystal structures deposi...

Structure validation is a crucial component not only in protein crystallography but also in model quality estimation in homology modeling, protein design and de-novo structure prediction. Two key attributes of a correctly determined atomic model are optimal packing between side-chains and absence of destabilizing unbalanced electric fields within t...

Local pseudo-unimolecular partial melting in polymeric cellular DNA is very much different from bimolecular comprehensive melting of short oligonucleotides in solutions. Several softwares estimate the melting temperature pretty accurately for the latter case and are used routinely for primer designing in PCR. However, the local partial melting in p...

Complementarity, in terms of both shape and electrostatic potential, has been quantitatively estimated at protein-protein interfaces and used extensively to predict the specific geometry of association between interacting proteins. In this work, we attempted to place both binding and folding on a common conceptual platform based on complementarity....

Figure S2. Motifs belonging to families f3a and f3b. Network diagrams of motifs up to size 7 (nodes) belonging to family f3a (left panel) and f3b (right). Motif identifier for each motif is displayed below the motif with the number of members for ASCN and APCN respectively in parentheses separated by a front slash.

Figure S4. Motifs belonging to family f5. Network diagrams of motifs up to size 7 (nodes) belonging to family f5. Motif identifier for each motif is displayed below the motif with the number of members for ASCN and APCN respectively in parentheses separated by a front slash.

Table S2. Distribution of networks by size amongst protein classes. The top row contains the fraction of the polypeptide chains in each class (bold in parenthesis). Along with frequency, the propensity (see Methods, section: propensity) of the network of a given size to be found in a particular class (enclosed in parenthesis) is also given.

Table S1. List of proteins with very large networks. Accession number (PDB ID), protein-class, polypeptide chain length, network size, fold, overall description of the protein and the source organism have been tabulated for each protein.

Table S3. Correlation between number of (unique) motifs: observed in the database versus simulated from random graphs. For a given network size (n), the number of unique motifs observed in the database is tabulated along with the corresponding number generated from simulated random graphs without and with cutoffs on the highest attainable degree of...

Figure S3. Motifs belonging to families f4a, f4b and f4c. Network diagrams of motifs up to size 7 (nodes) belonging to family f4a (left panel), f4b (middle) and f4c (right). Motif identifier for each motif is displayed below the motif with the number of members for ASCN and APCN respectively in parentheses separated by a front slash.

Dataset S1. Surface contact networks constituted of 15 nodes resolved into optimal set of motifs. Network diagrams of 38 contact networks of size 15 (ASCN) resolved into optimum sets of motifs (or variants) which are either components (separated by boxes) or induced subgraphs (highlighted with different colors). Families of these motifs are also me...

Figure S7. Optimally superposed triangles. Triangles (formed by joining the origins of the internal frames based on the three residues in a triplet clique) sampled from compositions belonging to categories C1 (all three residues different: top left), C2 (two residues identical: bottom left) and C3 (all three residues identical: right) superposed on...

Table S7: Links constituting the subset {Lcyp}: {Lcyp} represents the subset of links in the surface contact network of 2HAQ which is highly conserved among its close homologues defining the (cyclophilin-like) fold specific subgraph. Sec str represents the location of these links with respect to secondary structural elements and lp stands for the f...

Figure S1. Distribution of point atom contact networks according to size. Frequency distribution of networks of different sizes (n) for APCN follows a power law decay (Corresponding histogram is displayed in the inset, the X axis being truncated to n = 50).

Table S6. Triplet cliques constituted of hydrophobic residues exhibit preferences in their amino acid composition. Frequency distributions of triplet clique compositions in categories (a) C1 (all three residues different), (b) C2 (two residues identical) and (c) C3 (all three identical) are tabulated respectively.

Table S9. The Database. Polypeptide chains used in the analysis sorted according to class. The accession numbers (PDB ID), chain identifiers along with resolution in Angstroms and the first and last residue numbers (in case of multidomain proteins) are given in parenthesis.

Figure S5. Motifs belonging to families f6a, f6b and f7. Network diagrams of motifs up to size 7 (nodes) belonging to family f6a (left panel), f6b (middle) and f7 (right). Motif identifier for each motif is displayed below the motif with the number of members for ASCN and APCN respectively in parentheses separated by a front slash.

Table S4. Distribution of motifs and families in each protein-class. Motifs (obtained from ASCN, Sm > = 0.4, Ov > = 0.08) are sorted according to size (up to 7 nodes) and grouped under their respective families. The frequency of their occurrence is given along with the propensity (see Methods, section: propensity) of a given class to contain a fami...

Figure S6. Motifs belonging to families f8a, f8b and f8c. Network diagrams of motifs up to size 7 (nodes) belonging to family f8a (left panel), f8b (middle) and f8c (right). Motif identifier for each motif is displayed below the motif with the number of members for ASCN and APCN respectively in parentheses separated by a front slash.

Table S5. Distribution of motifs and families obtained at different contact cutoffs. Motifs are sorted according to size (up to 7 nodes) and grouped under their respective families. Cutoffs on Sm and Ov are mentioned in parenthesis. Results for the chosen set of cutoff values, used in the analysis (0.4, 0.08) are highlighted in bold.