Andrey A Gorin

Andrey A Gorin
Oak Ridge National Laboratory | ORNL · Computer Science and Mathematics Division

Ph D

About

69
Publications
3,722
Reads
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4,015
Citations
Citations since 2016
0 Research Items
610 Citations
2016201720182019202020212022020406080100
2016201720182019202020212022020406080100
2016201720182019202020212022020406080100
2016201720182019202020212022020406080100
Additional affiliations
January 2003 - December 2009
Oak Ridge National Laboratory
Position
  • Senior Research Staff Member
January 1997 - December 2002

Publications

Publications (69)
Article
In this paper, we propose a new hybrid scheme of parallel tempering and simulated annealing (hybrid PT/SA). Within the hybrid PT/SA scheme, a composite system with multi- ple conformations is evolving in parallel on a temperature ladder with various transition step sizes. The simulated annealing (SA) process uses a cooling scheme to decrease the te...
Article
Parallel tempering (PT), also known as replica exchange, is a powerful Markov Chain Monte Carlo sampling approach, which aims at reducing the relaxation time in simulations of physical systems. In this paper, we present a novel decentralized parallel implementa- tion of PT using the message passing interface (MPI) and the scalable parallel random n...
Article
A peptide-linkage deletion procedure is introduced for extracting the quantum mechanical (QM) interaction energies of individual groups in a complex environment and applied for the determination of the energetic contributions of the individual hydrogen bond acceptors (C=O's) and donors (N-H's) in parallel beta-sheets. For the beta-sheets studied he...
Article
Full-text available
With some simplifications, computational protein folding can be understood as an optimization problem of a potential energy function on a variable space consisting of all conformation for a given protein molecule. It is well known that realistic energy potentials are very "rough" functions, when expressed in the standard variables, and the folding...
Conference Paper
Full-text available
Mass-spectrometry (MS) is a powerful experimental technology for ”sequencing” proteins in complex biological mixtures. Computational methods are essential for the interpretation of MS data, and a number of theoretical questions remain unresolved due to intrinsic complexity of the related algorithms. Here we design an analytical approach to estimate...
Article
Full-text available
Protein-protein interactions are ubiquitous and essential for all cellular processes. High-resolution X-ray crystallographic structures of protein complexes can reveal the details of their function and provide a basis for many computational and experimental approaches. Differentiation between biological and non-biological contacts and reconstructio...
Article
Biological breakthroughs that can lead to improved diagnosis and treatment of diseases, generation of clean energy, and solutions to other critical societal problems require high performance, data-intensive computational tools that have the ability to process, analyze and cohesively integrate massive amounts of data and information in real time. Bi...
Conference Paper
Full-text available
Parallel Tempering (PT), also known as Replica Exchange, is a powerful Markov Chain Monte Carlo sampling approach which aims at reducing the relaxation time in simulations of physical systems. In this paper, we present a novel implementation of PT, so-called decentralized replica exchange PT, using MPI and the Scalable Parallel Random Number Genera...
Article
Computational prediction of protein complex structures through docking offers a means to gain a mechanistic understanding of protein interactions that mediate biological processes. This is particularly important as the number of experimentally determined structures of isolated proteins exceeds the number of structures of complexes. A comprehensive...
Article
It is believed that the binding of pyrimidin-2-one to cytosine deaminase (CD) leads to the formation of 4-[R]-hydroxyl-3,4-dihydropyrimidine (DHP). Here the formation of transition-state analogue (TSA) at the active site of yeast cytosine deaminase (yCD) is investigated by quantum mechanical/molecular mechanical (QM/MM) molecular dynamics (MD) and...
Article
Full-text available
Understanding the structure and dynamics of large biomolecular assemblies requires the development of new computational methods for (i) accurate structure prediction, (ii) molecular docking and (iii) long time-frame molecular simulation, and implementation on massively parallel computing infrastructure. This paper reviews our progress in these area...
Article
Full-text available
Parallel Tempering (PT) is an effective algorithm to overcome the slow convergence in low-temperature protein simulation by initiating multiple systems to run at multiple temperature levels and randomly switch with neighbor temperature levels. We implemented the PT scheme in the Rosetta to explore the rough energy landscape in protein folding and t...
Article
We derive the optimal number of peaks (defined as the minimum number that provides the required efficiency of spectra identification) in the theoretical spectra as a function of (i) the experimental accuracy, sigma, of the measured ratio m/z; (ii) experimental spectrum density; (iii) size of the database; (iv) number of peaks in the theoretical spe...
Conference Paper
Full-text available
Recently, we introduced probability profile method (PPM), which utilizes neutral-loss neighborhoods around each peak in MS/MS spectrum to "label" it: to assign a probability that the peak in question belongs to one of the specific categories (such as b- or y-ion peaks). Here we present the PPM-chain program - a PPM-based tool for de novo protein ta...
Conference Paper
Tandem mass spectrometry (MS/MS) is one of the leading proteomics technologies, applicable to a wide range of experiments involving composition analysis of protein mixtures. Currently only ∼10-20% of MS/MS spectral data lead to the successful peptide identifications, and the rate of false positives remains to be high. We propose probability profile...
Article
A growing body of evidence suggests a connection between protein dynamics and enzymatic catalysis. In this paper, we present a variety of computational studies designed to investigate the role of protein dynamics in the detailed mechanism of peptidyl-prolyl cis-trans isomerization catalyzed by human cyclophilin A. The results identify a network of...
Article
We propose a new stochastic global optimization method by accelerating the simulated tempering scheme with random walks executed on a temperature ladder with various transition step sizes. By suitably choosing the length of the transition steps, the accelerated scheme enables the search process to execute large jumps and escape entrapment in local...
Conference Paper
Full-text available
We note that a set of statistically "unusual" protein-profile pairs in experimentally determined database of protein-protein interactions can typify protein-protein interactions, and propose a novel method called PICUPP that sifts such protein-profile pairs using a statistical simulation. It is demonstrated that unusual Pfam and InterPro profile pa...
Conference Paper
Full-text available
A novel method is proposed for deciphering experimental tandem mass spectra. A large database of previously resolved peptide spectra was used to determine "neighborhood patterns" for each peak category: C- or N-terminus ions, their dehydrated fragments, etc. The established patterns are applied to assign probabilities for new spectra peaks to fit i...
Article
We report a new residual dipolar couplings (RDCs) based NMR procedure for rapidly determining RNA tertiary structure demonstrated on a uniformly (15)N/(13)C-labeled 27 nt variant of the trans-activation response element (TAR) RNA from HIV-I. In this procedure, the time-consuming nuclear Overhauser enhancement (NOE)-based sequential assignment step...
Article
DNA dodecamers of the alternating d(CG).d(CG) sequence with six phosphate groups either charge-neutralized or substituted by neutral methylphosphonates across the major or minor groove have been subjected to energy minimization to determine the conformational effect of the asymmetric elimination of phosphate charge. We report bending angles, direct...
Article
Full-text available
The U.S. Department of Energy recently announced the first five grants for the Genomes to Life (GTL) Program. The goal of this program is to "achieve the most far-reaching of all biological goals: a fundamental, comprehensive, and systematic understanding of life." While more information about the program can be found at the GTL website (www.doegen...
Article
Ground-state dynamics in RNA is a critical precursor for structural adaptation observed ubiquitously in protein-RNA recognition. A tertiary conformational analysis of the stem-loop structural element in the transactivation response element (TAR) from human immunodeficiency virus type 1 (HIV-I) RNA is presented using recently introduced NMR methods...
Article
We report on an NMR study of unlabeled and uniformly 13C,15N-labeled d(GAGCAGGT) sequence in 1 M NaCl solution, conditions under which it forms a head-to-head dimeric quadruplex containing sequentially stacked G-C-G-C, G-G-G-G and A-T-A-T tetrads. We have identified, for the first time, a slipped A-T-A-T tetrad alignment, involving recognition of W...
Article
We report the results of an NMR study of unlabeled and uniformly (13)C,(15)N-labeled d(G(3)AG(2)T(3)G(3)AT) in 100 mM NaCl, conditions under which it forms a dimeric quadruplex containing several new topological features. The DNA oligomer chain in each symmetry-related monomer subunit undergoes three sharp turns to form a compact domain, with all t...
Article
We present a new NMR procedure for determining the three-dimensional fold of C2-symmetric nucleic acid homodimers that relies on long-range orientational constraints derived from the measurement of two independent sets of residual dipolar couplings under two alignment conditions. The application is demonstrated on an (15)N/(13)C-enriched deoxyoligo...
Article
The non-steroidal anti-estrogen tamoxifen [TAM] has been in clinical use over the last two decades as a potent adjunct chemotherapeutic agent for treatment of breast cancer. It has also been given prophylactically to women with a strong family history of breast cancer. However, tamoxifen treatment has also been associated with increased endometrial...
Article
We have designed a DNA sequence, d(G-G-G-T-T-C-A-G-G), which dimerizes to form a 2-fold symmetric G-quadruplex in which G(syn). G(anti).G(syn).G(anti) tetrads are sandwiched between all trans G. (C-A) triads. The NMR-based solution structural analysis was greatly aided by monitoring hydrogen bond alignments across N-H...N and N-H...O==C hydrogen bo...
Article
We report on the identification of an A.(G.G.G.G).A hexad pairing alignment which involves recognition of the exposed minor groove of opposing guanines within a G.G.G.G tetrad through sheared G.A mismatch formation. This unexpected hexad pairing alignment was identified for the d(G-G-A-G-G-A-G) sequence in 150 mM Na(+) (or K(+)) cation solution whe...
Article
The Rex protein of the human T cell leukemia virus type 1 (HTLV-1) belongs to a family of proteins that use arginine-rich motifs (ARMs) to recognize their RNA targets. Previously, an in vitro selected RNA aptamer sequence was identified that mediates mRNA transport in vivo when placed in the primary binding site on stem-loop IID of the Rex response...
Article
The biological function of several viral and bacteriophage proteins, and their arginine-rich subdomains, involves RNA-mediated interactions. It has been shown recently that bound peptides adopt either beta-hairpin or alpha-helical conformations in viral and phage peptide-RNA complexes. We have compared the structures of the arginine-rich peptide do...
Article
Full-text available
Systematic, computer-simulated elongation of A- and B-DNA double helices beyond the range of normal room temperature fluctuations provides new insights into recent physical manipulations of single DNA molecules. The calculations include unusual states that are energetically disfavored under equilibrium conditions but that become favored as the DNA...
Article
Minor adducts, derived from the covalent binding of anti-benzo[a]pyrene-7,8-dihydroxy-9,10-epoxide to cellular DNA, may play an important role in generating mutations and initiating cancer. We have applied a combined NMR-computational approach including intensity based refinement to determine the solution structure of the minor (+)-cis-anti-[BP]dA...
Article
Solution structural studies have been undertaken on the aminopyrene-C(8)-dG ([AP]dG) adduct in the d(C5-[AP]G6-C7). d(G16-A17-G18) sequence context in an 11-mer duplex with dA opposite [AP]dG, using proton-proton distance and intensity restraints derived from NMR data in combination with distance-restrained molecular mechanics and intensity-restrai...
Article
A solution structural study has been undertaken on the aminofluorene-C8-dG ([AF]dG) adduct located at a single-strand-double-strand d(A1-A2-C3-[AF]G4-C5-T6-A7-C8-C9-A10-T11-C12-C13). d(G14-G15-A16-T17-G18-G19-T20- A21-G22-N23) 13/10-mer junction (N = C or A) using proton-proton distance restraints derived from NMR data in combination with intensity...
Article
Computer-simulated elongation and compression of A- and B-DNA structures beyond the range of thermal fluctuations provide new insights into high energy “activated” forms of DNA implicated in biochemical processes, such as recombination and transcription. All-atom potential energy studies of regular poly(dG)·poly(dC) and poly(dA)·poly(dT) double hel...
Article
While the majority of rheumatoid arthritis (RA) patients report that their pain is influenced by the weather, studies examining the impact of weather on RA pain have yielded equivocal results. It is not clear from the existing studies if the mixed results are due to limited statistical power (e.g. small sample sizes and restricted variability in we...
Article
We have applied NMR and molecular dynamics computations including intensity based refinement to define the structure of the d(G-G-G-C-T4-G-G-G-C) dodecanucleotide in 100 mM NaCl solution. The G-G-G-C sequence is of interest since it has been found as tandem repeats in the DNA sequence of human chromosome 19. The same G-G-G-C sequence is also seen a...
Article
Full-text available
The deformability of double helical DNA is critical for its packaging in the cell, recognition by other molecules, and transient opening during biochemically important processes. Here, a complete set of sequence-dependent empirical energy functions suitable for describing such behavior is extracted from the fluctuations and correlations of structur...
Article
We have determined the solution structure of a 15-mer boxB RNA hairpin complexed with a 20-mer basic peptide of the N protein involved in bacteriophage P22 transcriptional antitermination. Complex formation involves adaptive binding with the N peptide adopting a bent -helical conformation that packs tightly through hydrophobic and electrostatic int...
Article
We have determined the solution structure of a 15-mer boxB RNA hairpin complexed with a 20-mer basic peptide of the N protein involved in bacteriophage P22 transcriptional antitermination. Complex formation involves adaptive binding with the N peptide adopting a bent alpha-helical conformation that packs tightly through hydrophobic and electrostati...
Article
This paper addresses structural issues related to the capacity of aminofluorene [AF] for frameshift mutations of the -2 type on C8 covalent adduct formation at the G3 site in the d(C-G1-G2-C-G3-C-C) NarI hot spot sequence. This problem has been approached from a combined NMR and relaxation matrix analysis computational structural study of the [AF]d...
Article
A solution structural study has been undertaken on the aminofluorene-C8-dG ([AF]dG) adduct located at a single strand-double strand d(A1-A2-C3-[AF]G4-C5-T6-A7-C8-C9-A10-T11-C12-C13).d (G14-G15-A16-T17-G18-G19-T20-A 21-G22) 13/9-mer junction (designated [AF]dG 13/9-mer) using proton-proton distance and intensity restraints derived from NMR data in c...
Article
This study reports on the solution conformation of the covalent (+)-trans-anti-[BP]dG adduct (derived from the binding of the highly mutagenic and tumorigenic (+)-anti-benzo[a]pyrene diol epoxide to the N2 of deoxyguanosine) positioned opposite dC at a junctional site in the d(A1-A2-C3-[BP]G4-C5- T6-A7-C8-C9-A10-T11-C12-C13).d(G14-G15-A16-T17-+ ++G...
Article
A combined NMR-computational approach was employed to determine the solution structure of the (-)-trans-anti-[BP]dG adduct positioned opposite a -1 deletion site in the d(C1-C2-A3-T4-C5- [BP]G6-C7-T8-A9-C10-C11).d(G12-G13-T14-A15-G1 6-G17-A18-T19-G20-G21) sequence context. The (-)-trans-anti-[BP]dG moiety is derived from the binding of the (-)-anti...
Article
Earlier a three-dimensional model for a new unusual DNA conformation referred to as Slipped Loop Structure (SLS) has been suggested by us (1). The same type of folding could occur with RNA as well which means that one must use the A-form of the double helix rather than the B-one. The present paper discusses the creation of an all-atom stereochemica...
Article
Full-text available
High resolution chemical footprinting and cross-linking experiments have provided a basis for elucidating the overall architecture of the complex between the core DNA binding domain of p53 (p53DBD, amino acids 98–309) and the p21/waf1/cip1DNA response element implicated in the G1/S phase cell cycle checkpoint. These studies complement both a crysta...
Article
A combined NMR-molecular dynamics approach has been applied to determine the solution structure of a HIV-1 17-mer rev peptide bound to its 35-mer high affinity RNA aptamer binding site. Complex formation involves adaptive binding with the alpha-helical arginine-rich basic rev peptide targeting a widened RNA major groove centred about adjacent G.A a...
Article
A combined NMR-molecular dynamics approach has been applied to determine the solution structure of a HIV-117-mer rev peptide bound to its 35-mer high affinity RNA aptamer binding site. Complex formation involves adaptive binding with the -helical arginine-rich basic rev peptide targeting a widened RNA major groove centred about adjacent GA and reve...
Article
DNA base sequence, once thought to be interesting only as a carrier of the genetic blueprint, is now recognized as playing a structural role in modulating the biological activity of genes. Primary sequences of nucleic acid bases describe real three-dimensional structures with properties reflecting those structures. Moreover, the structures are base...
Article
Full-text available
The observed sequence dependence of the mean twist angles in 38 B-DNA crystal structures can be understood in terms of simple geometrical features of the constituent base-pairs. Structures with low twist appear to unwind in response to severe steric clashes of large exocyclic groups (such as NH2-NH2) in the major and minor grooves, while those with...
Article
Description of open CAN format (Compressed Amino acids and Nucleotides) is presented for storing genetic information in compressed form in data banks (DB). Data compression principles are demonstrated in detail on examples of EMBL DB (sequences of nucleotides), SWISSPROT DB (sequences of amino acids) and PDB DB (3D structures). A unified compressed...
Article
Short tandem repeats (5-8 base pairs) are not uncommon in the prokaryotic and eukaryotic DNA. Regions with such sequence motifs, when under superhelical stress, manifest unusual sensitivity to single-strand specific nuclease. To explain this, it has been suggested that one DNA thread should be shifted relatively to another, so that they could form...
Article
We have performed a conformational analysis of DNA double helices with parallel directed backbone strands. The calculations were made for homopolymers poly(dG).poly(dC). All possible models of base binding were checked. By the potential energy optimization the dihedral angles and helices parameters of stable conformations of parallel double polynuc...
Article
A method has been developed to solve structures of DNA oligomers in solution from the experimental NOE data. The method is a combination of two approaches: (1) full matrix NOESY simulations and (2) conformational calculations of DNA double helix based on generalized helical parameters. The process of the refinement of a solution structure does not...
Article
The ability of oligonucleotides 3'-d(GT)5pO(CH2)5Opd(GT)5-5' (anti[d(GT)]) and 3'-d(GT)5pO(CH2)6Opd(GT)5-3' (par[d(GT)]) to form hairpins and higher associates is studied. Optical methods of thermal denaturation and circular dichroism as well as the fluorescence of ethidium bromide and acridine orange bound to oligonucleotides were used. At room te...
Article
Full-text available
To investigate the influence of thermal fluctuations on DNA curvature the Metropolis procedure at 300 K was applied to B-DNA decamers containing A5.T5 and A4.T4 blocks. Monte Carlo simulations have confirmed the DNA bending anisotropy: B-DNA bends most easily in a groove direction (roll). The A5.T5 block is more rigid than the other sequences; the...
Article
A conformational transition of a single deoxyribose was analyzed in B-form trimers dA3:dT3 and dG3:dC3, both in the purine and pyrimidine chains. The main results were obtained for the duplexes with frozen ends, which could be extended by regular double helixes. The geometry of the central sugar ring in the duplexes may strongly deviate from the re...
Article
Full-text available
A computational approach that infers protein-protein interactions from genome sequences is proposed in this paper. It is based on our recent observation that protein-protein interactions can be identified by a set of "unusual" protein-profile pairs in experimentally determined protein interactions. A pair of protein-profiles is considered to be unu...
Article
This SAND report provides the technical progress through April 2005 of the Sandia-led project, ''Carbon Sequestration in Synechococcus Sp.: From Molecular Machines to Hierarchical Modeling'', funded by the DOE Office of Science GenomicsGTL Program. Understanding, predicting, and perhaps manipulating carbon fixation in the oceans has long been a maj...

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