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Introduction
My area of research, in general, involves theoretical and computational investigation of biomolecular complexes:
Sequence-structure-dynamics-function relations, vibrational collective dynamics of proteins with elastic network models, molecular dynamics simulations of proteins, protein binding site predictions, molecular docking, network of interactions within proteins via communication pathways, TCR-pHLA complex structures and their dynamics, virulence factors
Current institution
Additional affiliations
August 2010 - present
Position
- PhD Student
January 2010 - present
Publications
Publications (66)
Author Summary
Protein-protein interactions mediate, in essence, all inter- and intra-cellular processes. Thus, understanding their molecular mechanism is of utmost importance. Here we focus on one mechanistic aspect: differentiation between obligatory interactions, which persist throughout the entire lifetime of the protein complex, and non-oblig...
Atomistic molecular dynamics (MD) simulations generate a wealth of information related to the dynamics of proteins. If properly analyzed, this information can lead to new insights regarding protein function and assist wet-lab experiments. Aiming to identify interactions between individual amino acid residues and the role played by each in the conte...
Class I Major Histocompatibility Complex (MHC) binds short antigenic peptides with the help of Peptide Loading Complex (PLC), and presents them to T-cell Receptors (TCRs) of cytotoxic T-cells and Killer-cell Immunglobulin-like Receptors (KIRs) of Natural Killer (NK) cells. With more than 10000 alleles, human MHC (Human Leukocyte Antigen, HLA) is th...
The virulence factor Type IV pili (T4P) are surface appendages used by the opportunistic pathogen Pseudomonas aeruginosa for twitching motility and adhesion in the environment and during infection. Additionally, the use of these appendages by P. aeruginosa for biofilm formation increases its virulence and drug resistance. Therefore, attenuation of...
The production of β-lactamases is a prevalent mechanism that poses serious pressure on the control of bacterial resistance. Furthermore, the unavoidable and alarming increase in the transmission of bacteria producing extended-spectrum β-lactamases complicates treatment alternatives with existing drugs and/or approaches. Class D β-lactamases, design...
This study investigates the binding affinity and interaction mechanism of chlorhexidine (CHX), a commonly used antimicrobial agent, with lysozyme (LZM), a crucial salivary enzyme in the oral cavity. Chicken egg white lysozyme (CEWLZM) was used as a model LZM. Tri‐N‐acetylchitotriose (NAG3) was applied in redocking analysis to determine the exact bi...
Proteins like albumin are found in various environmental, living systems, and applications. It is known that functional, conformational and sorption properties of proteins are significantly affected by various surrounding conditions...
Virulence is an organism’s ability to infect the host and cause disease, and this ability is determined by the presence of virulence factors. The “do not kill, neutralize” strategy used by antivirulence therapies is a novel approach to managing the increasing drug resistance. In this respect, type IV pilus is one druggable target among many virulen...
In this study, the binding behavior of β‐sitosterol with lysozyme (LZM) was elucidated by surface plasmon resonance (SPR), computational molecular docking and molecular dynamics simulation studies. Chicken egg white lysozyme (CEWLZM) served as a model protein. Tri‐N‐acetylchitotriose (NAG3) was used in the redocking experiments to generate precise...
Lysozyme (LZM) is an important enzyme in medicine and industry. Tannic acid (TA) is used in brewing, wine industry, and as a food flavor enhancer. In nutritional and food science, LZM interacts with TA, notably in wine and saliva. This study aimed to investigate the binding interaction between LZM and TA using surface plasmon resonance, molecular d...
Lung adenocarcinoma (LUAD) is a significant planetary health challenge with its high morbidity and mortality rate, not to mention the marked interindividual variability in treatment outcomes and side effects. There is an urgent need for robust systems biomarkers that can help with early cancer diagnosis, prediction of treatment outcomes, and design...
HLA‐B*39:06, HLA‐B*39:01, and HLA‐B*38:01 are closely related HLA allotypes differentially associated with type 1 diabetes (T1D) risk and progression. B*39:06 is highly predisposing, while B*39:01 and B*38:01 are weakly predisposing and protective allotypes, respectively. Here, we aimed to decipher molecular mechanisms underlying the differential a...
Background/aim: The complicated nature of tumor formation makes it difficult to identify discriminatory genes. Recently, transcriptome-based supervised classification methods using support vector machines (SVMs) have become popular in this field. However, the inclusion of less significant variables in the construction of classification models can l...
Single nucleotide variations (SNVs) or variants are the common origin of alterations in human genome having exclusive functional roles in cell such as gene expression, disease susceptibility, and protein-protein interactions. These alterations might cause structural and dynamic impacts on proteins. Cancer is a heterogenous disease including abnorma...
The recurrent evolution of resistance to cardiotonic steroids (CTS) across diverse animals most frequently involves convergent amino-acid substitutions in the H1-H2 extracellular loop of Na+, K + -ATPase (NKA). Previous work revealed that hystricognath rodents (e.g. chinchilla) and pterocliform birds (sandgrouse) have convergently evolved amino-aci...
Type IV (T4) pilus is among the virulence factors with a key role in serious bacterial diseases. Specifically, in Neisseria meningitidis and Pseudomonas aeruginosa, it determines pathogenicity and causes infection. Here, a computational approach has been pursued to find piperidine-based inhibitor molecules against the elongation ATPase of T4 pili i...
The recurrent evolution of resistance to cardiotonic steroids (CTS) across diverse animals most frequently involves convergent amino-acid substitutions to the H1-H2 extracellular loop of Na+,K+-ATPase (NKA). Previous work established that hystricognath rodents (e.g. chinchilla) and pterocliform birds (sandgrouse) have convergently evolved amino-aci...
The connection of Epstein Barr virus (EBV) with diseases such as Burkitt Lymphoma, Hodgkin disease, multiple sclerosis, systemic lupus erythematosus and various B-cell lymphomas made EBV glycoproteins one of the most popular vaccine immunogens. As a protein being encoded by EBV, the viral membrane envelope protein gp350 is studied extensively due t...
Single nucleotide variants (SNVs) are single base substitutions that could influence many biological functions in the cell including gene expression, protein folding, and protein-protein interactions among many others. Thus, predictions of functional effects of cancer-related variants are crucial for drug responses and treatment options in clinical...
Cysteine dioxygenase (CDO) regulates the concentration of l-cysteine substrate by its oxidation in the body to prevent different diseases, including neurodegenerative and autoimmune diseases. CDO catalyzes the oxidation of thiol group of l-cysteine to l-cysteine sulfinic acid using molecular oxygen. In this study, molecular dynamics simulations wer...
The identification of biomolecules associated with papillary thyroid cancer (PTC) has upmost importance for the elucidation of the disease mechanism and the development of effective diagnostic and treatment strategies. Despite particular findings in this regard, a holistic analysis encompassing molecular data from different biological levels has be...
There is a critical requirement for alternative strategies to provide the better treatment in colorectal cancer (CRC). Hence, our goal was to propose novel biomarkers as well as drug candidates for its treatment through differential interactome based drug repositioning. Differentially interacting proteins and their modules were identified, and thei...
The rapidly increasing resistance to available antibiotics and the reduced rate in new antibiotic discovery lead to different therapeutic approaches. An attractive strategy is to identify molecules that target bacterial virulence as an alternative to traditional antibiotics with low efficacies. Anti-virulence therapies cleanse the pathogens from th...
Single nucleotide variations (SNVs) are the most widespread cause of alterations in human DNA, and they could play exclusive functional roles in the cell processes such as gene expression, disease susceptibility, and protein-protein interactions. The phenotypic consequences of SNVs can be neutral or negative effect on protein function or structure....
Antigen presentation by major histocompatibility complex (MHC) proteins to T-cell receptors (TCRs) plays a crucial role in triggering the adaptive immune response. Most of our knowledge on TCR-peptide-loaded major histocompatibility complex (pMHC) interaction stemmed from experiments yielding static structures, yet the dynamic aspects of this molec...
The resistance of microbes to commonly used antibiotics has become a worldwide health problem. A major underlying mechanism of microbial antibiotic resistance is the export of drugs from bacterial cells. Drug efflux is mediated through the action of multidrug resistance efflux pumps located in the bacterial cell membranes. The critical role of bact...
Nowadays, the rapid spread of bacterial diseases and the inability to prevent it, is a big problem. The rapidly increasing resistance to antibiotics that are used in the treatment of these diseases and the slowing down of the discovery of antibiotic classes leads to different therapeutic approaches [1], [2]. An inviting strategy is to identify mole...
Single-nucleotide polymorphisms (SNPs) are single-base variants that contribute to human biological variation and pathogenesis of many human diseases. Among all SNP types, nonsynonymous single-nucleotide polymorphisms (nsSNPs) can alter many structural, biochemical, and functional features of a protein such as folding characteristics, charge distri...
CREB-binding protein (CBP) is a multi-subunit scaffold protein complex in transcription regulation process, binding and interacting with ligands such as mixed-lineage leukemia (MLL) and c-Myb allosterically. Here in this study, we have revisited the concept of allostery in CBP via residue-based interaction energy calculation based on molecular dyna...
Artificial intelligence, machine learning, health care robots, and algorithms for clinical decision-making are currently being sought after in diverse fields of clinical medicine and bioengineering. The field of personalized medicine stands to benefit from new technologies so as to harness the omics big data, for example, to individualize and accel...
BACKGROUND: CREB binding protein is a scaffold protein in transcription process that is important for the regulation of RNA polymerase mediated transcription. In CBP, there are seven folded interacting domains that assemble. A multi protein machinery in binding with several transcription factors, signaling molecules and hormone receptors. One of th...
Telomeres, and telomere length in particular, have broad significance for genome biology and thus are prime research targets for complex diseases such as cancers. In this context, BRCA1 and BRCA2 gene mutations have been implicated in relationship to telomere length, and breast cancer susceptibility. Yet, the linkages among human genetic variation...
Class I Major Histocompatibility Complex (MHC) binds short antigenic peptides with the help of Peptide Loading Complex (PLC), and presents them to T-cell Receptors (TCRs) of cytotoxic T-cells and Killer-cell Immunglobulin-like Receptors (KIRs) of Natural Killer (NK) cells. With more than 10000 alleles, the Human Leukocyte Antigen (HLA) chain of MHC...
Major Histocompatibility Complex (MHC) is a cell surface glycoprotein that binds to foreign antigens and presents them to T lymphocyte cells on the surface of Antigen Presenting Cells (APCs) for appropriate immune recognition. Recently, studies focusing on peptide-based vaccine design have allowed a better understanding of peptide immunogenicity me...
ProSNEx (Protein Structure Network Explorer) is a web service for construction and analysis of Protein Structure Networks (PSNs) alongside amino acid flexibility, sequence conservation and annotation features. ProSNEx constructs a PSN by adding nodes to represent residues and edges between these nodes using user-specified interaction distance cutof...
Hücre yüzey glikoproteinleri olan Temel Doku Uygunluk Kompleks (MHC) molekülleri yabancı antijenlere bağlanır ve onları uygun immün tanınma için antijen sunucu hücrelerin yüzeyindeki T lenfosit hücrelerine sunar. İlk olarak insanlarda lökosit hücrelerinde tanımlanmış oldukları için, aynı zamanda İnsan Lökosit Antijenleri (HLA) olarak da isimlendiri...
Caspases are members of a highly regulated aspartate-cysteine protease family which have important roles in apoptosis. Pharmaceutical studies focused on these molecules since they are involved in diseases such as cancer and neurodegenerative disorders. A small molecule which binds to the dimeric interface away from the binding site induces a confor...
Biyolojik sistemler, birbirleri ile sürekli bilgi alışverişinde
bulunan ağyapılar, biyolojik moleküller de bu yapının temel
noktaları olarak tanımlanabilirler. Yaşamsal süreklilik açısından
sistemin herhangi bir noktasında oluşacak bir sinyalin, hücreler
arasında, hücre içinde veya hücre dışından hücre içine iletilmesi
büyük önem taşımaktadır. Bu ç...
We report a tool for efficient computation and characterization of pairwise amino acid residue interaction energies from MD simulations
Human Major Histocompatibility Complex class I (MHC I) –or Human Leukocyte Antigen (HLA)- proteins present intracellularly processed peptides to cytotoxic T lymphocytes in the adaptive immune response to pathogens. A high level of polymorphism in human MHC I proteins defines the peptide-binding specificity of thousands of different MHC alleles. How...
Highly polymorphic Major Histocompatibility Complex (MHC, also termed Human Leukocyte Antigens, or HLA in humans) proteins bind peptide fragments generated as a result of the action of the proteasome machinery in Antigen Presenting Cells and present them on the cell surface to T-cell Receptor molecules. The flexibility profile of the molecular surf...
A single amino acid difference (Asp116His), having a key role in a pathogenesis pathway, distinguishes HLA-B*27:05 and HLA-B*27:09 sub-types as associated and non-associated with ankylosing spondylitis, respectively. In this study, molecular docking simulations were carried out with the aim of comprehending the differences in the binding behavior o...
Human Leukocyte Antigens (HLA) are highly polymorphic proteins that play a key role in the immune system. HLA molecule is present on the cell membrane of antigen-presenting cells of the immune system and presents short peptides, originating from the proteins of invading pathogens or self-proteins, to the T-cell Receptor (TCR) molecule of the T-cell...
Understanding the characteristic dynamics of different Human Leukocyte Antigen (HLA) alleles of the peptide-loaded Major Histocompatibility Complex (pMHC) may help explain mechanism of initial steps in T-cell activa-
tion. Molecular Dynamics (MD), as a fully atomistic simulation method, is commonly used to explain the functional effect of polymorph...
Peptide-loaded Major Histocompatibility Complex (pMHC) proteins play a key role in the transmission of molecular signals through the immune system via their interaction with T-cell receptors. Many alleles and sub-types of these proteins are found to be associated with autoimmune diseases; hence the importance of understanding the mechanism...
The dynamic behavior of peptide-loaded Major Histocompatibility Complex (pMHC) plays a role in defining the immunogenicity of the pMHC-T-cell Receptor interaction. However, due to the highly polymorphic nature of the antigen chain of the complex (Human Leukocyte Antigens, HLA) and the limitation of experimental and computational metho...
It is of significant interest to understand how proteins interact, which holds the key phenomenon in biological functions. Using dynamic fluctuations in high frequency modes, we show that the Gaussian Network Model (GNM) predicts hot spot residues with success rates ranging between S 8-58%, C 84-95%, P 5-19% and A 81-92% on unbound structures and S...
The CAPRI (Critical Assessment of Predicted Interactions) and CASP (Critical Assessment of protein Structure Prediction) experiments have demonstrated the power of community-wide tests of methodology in assessing the current state of the art and spurring progress in the very challenging areas of protein docking and structure prediction. We sought t...
DNABINDPROT is designed to predict DNA-binding residues, based on the fluctuations of residues in high-frequency modes by
the Gaussian network model. The residue pairs that display high mean-square distance fluctuations are analyzed with respect
to DNA binding, which are then filtered with their evolutionary conservation profiles and ranked accordi...
Instrumented three-point bend impact fracture tests are widely used to evaluate pipe grade polymers. Often specimens cut from small-diameter pipe are used, and these are necessarily arc-shaped. Because the orientation and thermal history may differ between extruded pipe and compression moulded plaque material, this additional difference in geometry...
Proteins are building units of genomes. There exist a correlation between sequence, structure and function of proteins, and function is closely related to structural dynamics. To understand how genomes and proteomes give rise to biological functions, it is necessary to go from the three to the fourth dimensional pictures of proteins; that is their...
Developers of polyethylene grades for pressure pipe seek a deeper understanding of the resistance of these materials to high rate, plane-stress fracture. The Reversed Charpy and ASTM F 2231 ''Thin Charpy'' test methods are designed to index this property, at appro-priately high rates, for quality control and material de-velopment purposes. This art...
The Rapid Crack Propagation régime in pressurised polyethylene pipe is limited by a critical temperature, which is determined mainly by the increasing resistance of the material to plane stress fracture. The Reversed Charpy and ASTM F2231 'Thin Charpy' test methods are designed to index this property, at appropriately high rates, for quality contro...
Proteins are building units of genomes. There exist a correlation between sequence, structure and function of proteins, and function is closely related to structural dynamics. To understand how genomes and proteomes give rise to biological functions, it is necessary to go from the three to the fourth dimensional pictures of proteins; that is their...
