Browsing by Author "Shakhnovich, Eugene"
Now showing items 1-20 of 53
-
All-Atom Model for Stabilization of α-Helical Structure in Peptides by Hydrocarbon Staples
Kutchukian, Peter S.; Yang, Jae Shick; Verdine, Gregory L.; Shakhnovich, Eugene Isaacovitch (American Chemical Society (ACS), 2009)Recent work has shown that the incorporation of an all-hydrocarbon “staple” into peptides can greatly increase their α-helix propensity, leading to an improvement in pharmaceutical properties such as proteolytic stability, ... -
Assessing the Effect of Loop Mutations in the Folding Space of β2-Microglobulin with Molecular Dynamics Simulations
Estácio, Sílvia G.; Shakhnovich, Eugene I.; Faísca, Patrícia F. N. (MDPI, 2013)We use molecular dynamics simulations of a full atomistic Gō model to explore the impact of selected DE-loop mutations (D59P and W60C) on the folding space of protein human β2-microglobulin (Hβ2m), the causing agent of ... -
Benchmarking Inverse Statistical Approaches for Protein Structure and Design with Exactly Solvable Models
Jacquin, Hugo; Gilson, Amy; Shakhnovich, Eugene; Cocco, Simona; Monasson, Rémi (Public Library of Science, 2016)Inverse statistical approaches to determine protein structure and function from Multiple Sequence Alignments (MSA) are emerging as powerful tools in computational biology. However the underlying assumptions of the relationship ... -
Biophysical principles predict fitness landscapes of drug resistance
Rodrigues, Joao Vierira; Bershtein, Shimon; Li, Annabel; Lozovsky, Elena; Hartl, Daniel L.; Shakhnovich, Eugene Isaacovitch (Proceedings of the National Academy of Sciences, 2016)Fitness landscapes of drug resistance constitute powerful tools to elucidate mutational pathways of antibiotic escape. Here, we de- veloped a predictive biophysics-based fitness landscape of trimeth- oprim (TMP) resistance ... -
A biophysical protein folding model accounts for most mutational fitness effects in viruses
Wylie, C; Shakhnovich, Eugene Isaacovitch (Proceedings of the National Academy of Sciences, 2011)Fitness effects of mutations fall on a continuum ranging from lethal to deleterious to beneficial. The distribution of fitness effects (DFE) among random mutations is an essential component of every evolutionary model and ... -
Catalysis of Protein Folding by Chaperones Accelerates Evolutionary Dynamics in Adapting Cell Populations
Çetinbaş, Murat; Shakhnovich, Eugene I. (Public Library of Science, 2013)Although molecular chaperones are essential components of protein homeostatic machinery, their mechanism of action and impact on adaptation and evolutionary dynamics remain controversial. Here we developed a physics-based ... -
Computer Simulations of Protein Folding and Evolution
Xu, Jiabin (2013-10-14)Computer simulations for investigating protein folding and evolution are presented. In chapter 1, an all-atom model with a knowledge-based potential is used to study the folding kinetics of Formin-Binding protein. We study ... -
Constraints Imposed by Non-Functional Protein–Protein Interactions on Gene Expression and Proteome Size
Zhang, Jingshan; Maslov, Sergei; Shakhnovich, Eugene Isaacovitch (Nature Publishing Group, 2008)Crowded intracellular environments present a challenge for proteins to form functional specific complexes while reducing non-functional interactions with promiscuous non-functional partners. Here we show how the need to ... -
Contribution of Selection for Protein Folding Stability in Shaping the Patterns of Polymorphisms in Coding Regions
Serohijos, Adrian W.R.; Shakhnovich, Eugene I. (Oxford University Press, 2013)The patterns of polymorphisms in genomes are imprints of the evolutionary forces at play in nature. In particular, polymorphisms have been extensively used to infer the fitness effects of mutations and their dynamics of ... -
DNA Unzipping Phase Diagram Calculated Via Replica Theory
Roland, C. Brian; Hatch, Kristi Adamson; Prentiss, Mara; Shakhnovich, Eugene Isaacovitch (American Physical Society, 2009)We show how single-molecule unzipping experiments can provide strong evidence that the zero-force melting transition of long molecules of natural dsDNA should be classified as a phase transition of the higher-order type ... -
ELISA: Structure-Function Inferences Based On Statistically Significant and Evolutionarily Inspired Observations
Shakhnovich, Boris E; Comeau, Steve; Lorenz, David; DeLisi, Charles; Harvey, John; Shakhnovich, Eugene Isaacovitch (BioMed Central, 2003)The problem of functional annotation based on homology modeling is primary to current bioinformatics research. Researchers have noted regularities in sequence, structure and even chromosome organization that allow valid ... -
Emergence of species in evolutionary “simulated annealing”
Heo, Muyoung; Kang, Louis; Shakhnovich, Eugene Isaacovitch (Proceedings of the National Academy of Sciences, 2009)Which factors govern the evolution of mutation rates and emergence of species? Here, we address this question by using a first principles model of life where population dynamics of asexual organisms is coupled to molecular ... -
Energetics of Protein–DNA Interactions
Donald, Jason E.; Chen, William Wei-Lun; Shakhnovich, Eugene Isaacovitch (Oxford University Press, 2007)Protein–DNA interactions are vital for many processes in living cells, especially transcriptional regulation and DNA modification. To further our understanding of these important processes on the microscopic level, it is ... -
The ensemble folding kinetics of the FBP28 WW domain revealed by an all-atom Monte Carlo simulation in a knowledge-based potential
Xu, Jiabin; Huang, Lei; Shakhnovich, Eugene Isaacovitch (Wiley-Blackwell, 2011)In this work, we apply a detailed all-atom model with a transferable knowledge-based potential to study the folding kinetics of Formin-Binding protein, FBP28, which is a canonical three-stranded β-sheet WW domain. Replica ... -
Entropic Stabilization of Proteins and Its Proteomic Consequences
Berezovsky, Igor N.; Chen, William W.; Choi, Paul J.; Shakhnovich, Eugene (Public Library of Science, 2005)Evolutionary traces of thermophilic adaptation are manifest, on the whole-genome level, in compositional biases toward certain types of amino acids. However, it is sometimes difficult to discern their causes without a clear ... -
A First-Principles Model of Early Evolution: Emergence of Gene Families, Species, and Preferred Protein Folds
Chen, Peiqiu; Zeldovich, Konstantin B.; Shakhnovich, Eugene; Shakhnovich, Boris E. (Public Library of Science, 2007)In this work we develop a microscopic physical model of early evolution where phenotype—organism life expectancy—is directly related to genotype—the stability of its proteins in their native conformations—which can be ... -
From The Cover: A simple physical model for scaling in protein-protein interaction networks
Deeds, E. J.; Ashenberg, O.; Shakhnovich, Eugene Isaacovitch (Proceedings of the National Academy of Sciences, 2005)It has recently been demonstrated that many biological networks exhibit a “scale-free” topology, for which the probability of observing a node with a certain number of edges (k) follows a power law: i.e., p(k) ∼ k -γ. This ... -
Graph’s Topology and Free Energy of a Spin Model on the Graph
Choi, Jeong-Mo; Gilson, Amy Ilana; Shakhnovich, Eugene Isaacovitch (American Physical Society (APS), 2017)In this work we show that there is a direct relationship between a graph's topology and the free energy of a spin system on the graph. We develop a method of separating topological and enthalpic contributions to the free ... -
Identification of the minimal protein-folding nucleus through loop-entropy perturbations
Lindberg, M. O.; Haglund, E.; Hubner, I. A.; Shakhnovich, Eugene Isaacovitch; Oliveberg, M. (Proceedings of the National Academy of Sciences, 2006)To explore the plasticity and structural constraints of the protein-folding nucleus we have constructed through circular permutation four topological variants of the ribosomal protein S6. In effect, these topological ... -
Improvisation in evolution of genes and genomes: whose structure is it anyway?
Shakhnovich, Boris E; Shakhnovich, Eugene Isaacovitch (Elsevier BV, 2008)Significant progress has been made in recent years in a variety of seemingly unrelated fields such as sequencing, protein structure prediction, and high-throughput transcriptomics and metabolomics. At the same time new ...