A5038256975- Protein Structure and Dynamics
- Enzyme Structure and Function
- HIV/AIDS drug development and treatment
- HIV Research and Treatment
- Material Dynamics and Properties
- RNA and protein synthesis mechanisms
- Lipid Membrane Structure and Behavior
- Bacterial Genetics and Biotechnology
- Cystic Fibrosis Research Advances
- Computational Drug Discovery Methods
- DNA and Nucleic Acid Chemistry
- Polymer crystallization and properties
- Bioinformatics and Genomic Networks
- Theoretical and Computational Physics
- Advanced NMR Techniques and Applications
- Block Copolymer Self-Assembly
- Microbial Metabolic Engineering and Bioproduction
- Molecular Communication and Nanonetworks
- Mass Spectrometry Techniques and Applications
- Advanced biosensing and bioanalysis techniques
- Force Microscopy Techniques and Applications
- Drug Transport and Resistance Mechanisms
- Ion channel regulation and function
- Machine Learning in Bioinformatics
- Advanced Polymer Synthesis and Characterization
Boğaziçi University
2016-2025
Scientific and Technological Research Council of Turkey
1995-2023
University of Pittsburgh
2015
Tel Aviv University
2010-2012
Koç University
2010
University of Akron
1994-2000
National Institutes of Health
1997
National Cancer Institute
1997
Vibrational dynamics of folded proteins is studied using a Gaussian model in which the protein viewed as network, residues representing junctions, and connectivity being established by single parameter harmonic potential. Application to seven showed that local packing density plays major role determining vibrational spectrum at time scales picoseconds. At later times, secondary structure tertiary context each residue comes into play. The frequencies obey universal distribution, confirming...
Abstract Proteins are highly flexible molecules. Prediction of molecular flexibility aids in the comprehension and prediction protein function providing details functional mechanisms. The ability to predict locations, directions, extent movements can assist fitting atomic resolution structures low‐resolution EM density maps predicting complex interacting molecules (docking). There several types movements. In this work, we focus on hinge Given a single structure, method automatically divides...
The development of HIV-1 protease inhibitors has been the historic paradigm rational structure-based drug design, where structural and thermodynamic analyses have assisted in discovery novel inhibitors. While total enthalpy entropy change upon binding determine affinity, often thermodynamics are considered terms inhibitor properties only. In current study, profound changes observed a drug-resistant variant compared to wild-type protease, irrespective bound. This (Flap+) combination flap...
Allosteric mechanism of proteins is essential in biomolecular signaling. An important aspect underlying this the communication pathways connecting functional residues. Here, a Monte Carlo (MC) path generation approach proposed and implemented to define likely allosteric through generating an ensemble maximum probability paths. The protein structure considered as network amino acid residues, inter-residue interactions are described by atomistic potential function. PDZ domain structures...
Abstract Transition metals (e.g., Fe 2/3+ , Zn 2+ Mn ) are essential enzymatic cofactors in all organisms. Their environmental scarcity led to the evolution of high‐affinity uptake systems. Our research focuses on two bacterial manganese ABC importers, Streptococcus pneumoniae PsaBC and Bacillus anthracis MntBC, both critical for virulence. Both importers share a similar homodimeric structure, where each protomer comprises transmembrane domain (TMD) linked cytoplasmic nucleotide‐binding...
An analytical approach based on Gaussian network model (GNM) is proposed for predicting the rotational dynamics of proteins. The method, previously shown to successfully reproduce X-ray crystallographic temperature factors a series proteins extended here predict bond torsional mobilities and reorientation main chain amide groups probed by 15N-H nuclear magnetic resonance (NMR) relaxation. hen egg-white lysozyme (HEWL) in folded state investigated using approach. Excellent agreement observed...
The exchange dynamics of chains between micelles diblock copolymers in dilute solution a selective solvent has been studied by semianalytical approach. A close inspection dynamic Monte Carlo simulation trajectories showed that there are mainly two types mechanisms, chain insertion/expulsion and micellar merger/splitting. relative contributions the mechanisms to overall examined as function following variables: concentration copolymers, energy interaction insoluble block surroundings, size...
DNABINDPROT is designed to predict DNA-binding residues, based on the fluctuations of residues in high-frequency modes by Gaussian network model. The residue pairs that display high mean-square distance are analyzed with respect DNA binding, which then filtered their evolutionary conservation profiles and ranked according propensities. If analyses exact outcome highest mode, using a threshold 5, results have sensitivity, specificity, precision accuracy 9.3%, 90.5%, 18.1% 78.6%, respectively,...
The trimeric human copper transporter 1 (hCTR1) is essential for uptake and implicated in sensitivity to chemotherapy drugs. Using the cryoelectron microscopy (cryoEM) map of hCTR1 evolutionary data, we constructed a Cα-trace model membrane region. structure, supported by mutagenesis was used investigate global dynamics through elastic network models. Identified as dominant hinge regions, hCTR1’s MxxxM GxxxG motifs were shown have significant roles functional movements characterized two...
The KIX domain of CBP is a transcriptional coactivator. Concomitant binding to the activation proto-oncogene protein c-Myb and transactivation trithorax group mixed lineage leukemia (MLL) transcription factor lead biologically active ternary MLL∶KIX∶c-Myb complex which plays role in Pol II-mediated transcription. MLL enhances binding. Here we carried out molecular dynamics (MD) simulations for complex, its binary components with goal providing mechanistic explanation experimental...
It is of significant interest to understand how proteins interact, which holds the key phenomenon in biological functions. Using dynamic fluctuations high frequency modes, we show that 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 8-51%, 97-99%, 14-50%, 94-97% complex for sensitivity, specificity, precision accuracy, respectively. High specificity accuracy a single property protein...
Abstract Motivation Allostery in proteins is an essential phenomenon biological processes. In this article, we present a computational model to predict paths of maximum information transfer between active and allosteric sites. theoretic study, use mutual as the measure transfer, where transition probability from one residue its contacting neighbors proportional magnitude two residues. Starting given using Hidden Markov Model, successively determine neighboring residues that eventually lead...
Abstract Motivation Proteins are dynamic entities that undergo conformational changes critical for their functions. Understanding the communication pathways and information transfer within proteins is crucial elucidating allosteric interactions in mechanisms. This study utilizes mutual (MI) analysis to probe allostery. Using two cases, Ubiquitin PLpro, we have evaluated accuracy limitations of different approximations including exact anisotropic isotropic models, multivariate Gaussian model,...
Residues at the binding sites of ligand and receptor several enzyme-inhibitor antibody-antigen complexes are predicted from slowest (for ligand) fastest receptor) modes motion by Gaussian Network Model applied to unbound molecules.
The Gaussian network model is used to derive the correlations between energy and residue fluctuations in native proteins. Residues are identified that respond strongly display with remaining residues of protein at highest modes. We postulate these located specific sites for drug binding. test validity this on a data set 33 structurally distinct proteins unbound state. Detailed results presented binding HIV protease.