Browsing by Author "Shakhnovich, Eugene"
Now showing items 21-40 of 53
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The Influence of Selection for Protein Stability on dN/dS Estimations
Dasmeh, Pouria; Serohijos, Adrian W.R.; Kepp, Kasper P.; Shakhnovich, Eugene I. (Oxford University Press, 2014)Understanding the relative contributions of various evolutionary processes—purifying selection, neutral drift, and adaptation—is fundamental to evolutionary biology. A common metric to distinguish these processes is the ... -
Influenza A H1N1 Pandemic Strain Evolution – Divergence and the Potential for Antigenic Drift Variants
Klein, Eili Y.; Serohijos, Adrian W. R.; Choi, Jeong-Mo; Shakhnovich, Eugene I.; Pekosz, Andrew (Public Library of Science, 2014)The emergence of a novel A(H1N1) strain in 2009 was the first influenza pandemic of the genomic age, and unprecedented surveillance of the virus provides the opportunity to better understand the evolution of influenza. We ... -
Interplay between Pleiotropy and Secondary Selection Determines Rise and Fall of Mutators in Stress Response
Heo, Muyoung; Shakhnovich, Eugene Isaacovitch (Public Library of Science (PLoS), 2010)Mutators are clones whose mutation rate is about two to three orders of magnitude higher than the rate of wild-type clones and their roles in adaptive evolution of asexual populations have been controversial. Here we address ... -
Isolation and Analysis of Rare Norovirus Recombinants from Coinfected Mice Using Drop-Based Microfluidics
Zhang, Huidan; Cockrell, Shelley K.; Kolawole, Abimbola O.; Rotem, Assaf; Serohijos, Adrian; Chang, Connie B.; Tao, Ye; Mehoke, Thomas S.; Han, Yulong; Lin, Jeffrey S.; Giacobbi, Nicholas S.; Feldman, Andrew B.; Shakhnovich, Eugene Isaacovitch; Weitz, David A.; Wobus, Christiane E.; Pipas, James M. (American Society for Microbiology, 2015)Human noroviruses (HuNoVs) are positive-sense RNA viruses that can cause severe, highly infectious gastroenteritis. HuNoV outbreaks are frequently associated with recombination between circulating strains. Strain genotyping ... -
A macroscopic device described by a Boltzmann-like distribution
Tricard, Simon; Stan, Claudiu A.; Shakhnovich, Eugene Isaacovitch; Whitesides, George McClelland (Royal Society of Chemistry (RSC), 2013)Equilibrium thermodynamic phenomena such as the Maxwell-Boltzmann distribution of molecular velocities are rare in systems of macroscopic particles interacting by mechanical collisions. This paper reports a system composed ... -
Mechanical Model of Globular Transition in Polymers
Tricard, Simon; Shepherd, Robert F.; Stan, Claudiu A.; Snyder, Phillip W.; Cademartiri, Rebecca; Zhu, Danny; Aranson, Igor S.; Shakhnovich, Eugene Isaacovitch; Whitesides, George McClelland (Wiley-Blackwell, 2014)In complex, multicomponent systems, polymers often undergo phase transitions between distinct conformations. This paper reports a millimeter-scale granular model of coil-to-globule transitions: one “polymer” chain—a ... -
Merging molecular mechanism and evolution: theory and computation at the interface of biophysics and evolutionary population genetics
Serohijos, Adrian; Shakhnovich, Eugene Isaacovitch (Elsevier BV, 2014)The variation among sequences and structures in nature is both determined by physical laws and by evolutionary history. However, these two factors are traditionally investigated by disciplines with different emphasis and ... -
Multi-Scale Theoretical Investigations of Protein Interactions and Evolution
Choi, Jeong-Mo (2016-05-12)Evolution of biological systems requires players of multiple layers, from atoms and molecules to organisms and populations. Expression of a gene is operated by molecular machineries for transcription, translation, regulation, ... -
Mutation Induced Extinction in Finite Populations: Lethal Mutagenesis and Lethal Isolation
Wylie, Christopher Scott; Shakhnovich, Eugene Isaacovitch (Public Library of Science, 2012)Reproduction is inherently risky, in part because genomic replication can introduce new mutations that are usually deleterious toward fitness. This risk is especially severe for organisms whose genomes replicate ... -
On the origin and highly likely completeness of single-domain protein structures
Zhang, Y.; Hubner, I. A.; Arakaki, A. K.; Shakhnovich, Eugene Isaacovitch; Skolnick, J. (Proceedings of the National Academy of Sciences, 2006)The size and origin of the protein fold universe is of fundamental and practical importance. Analyzing randomly generated, compact sticky homopolypeptide conformations constructed in generic simplified and all-atom protein ... -
Optimality of Mutation and Selection in Germinal Centers
Zhang, Jingshan; Shakhnovich, Eugene Isaacovitch (Public Library of Science (PLoS), 2010)The population dynamics theory of B cells in a typical germinal center could play an important role in revealing how affinity maturation is achieved. However, the existing models encountered some conflicts with experiments. ... -
PDB-UF: Database of Predicted Enzymatic Functions for Unannotated Protein Structures from Structural Genomics
von Grotthuss, Marcin; Plewczynski, Dariusz; Ginalski, Krzysztof; Rychlewski, Leszek; Shakhnovich, Eugene Isaacovitch (BioMed Central, 2006)The number of protein structures from structural genomics centers dramatically increases in the Protein Data Bank (PDB). Many of these structures are functionally unannotated because they have no sequence similarity to ... -
Positive and Negative Design in Stability and Thermal Adaptation of Natural Proteins
Berezovsky, Igor N.; Zeldovich, Konstantin B.; Shakhnovich, Eugene (Public Library of Science, 2007)The aim of this work is to elucidate how physical principles of protein design are reflected in natural sequences that evolved in response to the thermal conditions of the environment. Using an exactly solvable lattice ... -
Positively Selected Sites in Cetacean Myoglobins Contribute to Protein Stability
Dasmeh, Pouria; Serohijos, Adrian; Kepp, Kasper P.; Shakhnovich, Eugene Isaacovitch (Public Library of Science, 2013)Since divergence ∼50 Ma ago from their terrestrial ancestors, cetaceans underwent a series of adaptations such as a ∼10–20 fold increase in myoglobin (Mb) concentration in skeletal muscle, critical for increasing oxygen ... -
Predicting Specificity-Determining Residues in Two Large Eukaryotic Transcription Factor Families
Donald, Jason E.; Shakhnovich, Eugene Isaacovitch (Oxford University Press, 2005)Certain amino acid residues in a protein, when mutated, change the protein's function. We present an improved method of finding these specificity-determining positions that uses all the protein sequence data available for ... -
Protein and DNA Sequence Determinants of Thermophilic Adaptation
Zeldovich, Konstantin B.; Berezovsky, Igor N.; Shakhnovich, Eugene (Public Library of Science, 2007)There have been considerable attempts in the past to relate phenotypic trait—habitat temperature of organisms—to their genotypes, most importantly compositions of their genomes and proteomes. However, despite accumulation ... -
Protein Biophysics Explains Why Highly Abundant Proteins Evolve Slowly
Serohijos, Adrian; Rimas, Zilvinas; Shakhnovich, Eugene Isaacovitch (Elsevier BV, 2012)The consistent observation across all kingdoms of life that highly abundant proteins evolve slowly demonstrates that cellular abundance is a key determinant of protein evolutionary rate. However, other empirical findings, ... -
Protein Homeostasis Imposes a Barrier on Functional Integration of Horizontally Transferred Genes in Bacteria
Bershtein, Shimon; Serohijos, Adrian W. R.; Bhattacharyya, Sanchari; Manhart, Michael; Choi, Jeong-Mo; Mu, Wanmeng; Zhou, Jingwen; Shakhnovich, Eugene I. (Public Library of Science, 2015)Horizontal gene transfer (HGT) plays a central role in bacterial evolution, yet the molecular and cellular constraints on functional integration of the foreign genes are poorly understood. Here we performed inter-species ... -
Protein Homeostasis Imposes a Barrier on Functional Integration of Horizontally Transferred Genes in Bacteria
Bershtein, Shimon; Serohijos, Adrian W. R.; Bhattacharyya, Sanchari; Manhart, Michael; Choi, Jeong-Mo; Mu, Wanmeng; Zhou, Jingwen; Shakhnovich, Eugene I. (Public Library of Science, 2015)Horizontal gene transfer (HGT) plays a central role in bacterial evolution, yet the molecular and cellular constraints on functional integration of the foreign genes are poorly understood. Here we performed inter-species ... -
Protein Quality Control Acts on Folding Intermediates to Shape the Effects of Mutations on Organismal Fitness
Bershtein, Shimon; Mu, Wanmeng; Serohijos, Adrian; Zhou, Jingwen; Shakhnovich, Eugene Isaacovitch (Elsevier BV, 2012)What are the molecular properties of proteins that fall on the radar of protein quality control (PQC)? Here we mutate the E. coli’s gene encoding dihydrofolate reductase (DHFR) and replace it with bacterial orthologous ...