A5082765817- Protein Structure and Dynamics
- Enzyme Structure and Function
- RNA and protein synthesis mechanisms
- Theoretical and Computational Physics
- Material Dynamics and Properties
- Bioinformatics and Genomic Networks
- Microbial Metabolic Engineering and Bioproduction
- Evolution and Genetic Dynamics
- Genomics and Phylogenetic Studies
- Mass Spectrometry Techniques and Applications
- Connexins and lens biology
- RNA Research and Splicing
- Machine Learning in Bioinformatics
- Block Copolymer Self-Assembly
- Bacterial Genetics and Biotechnology
- Spectroscopy and Quantum Chemical Studies
- Gene Regulatory Network Analysis
- Heat shock proteins research
- Computational Drug Discovery Methods
- RNA modifications and cancer
- Bacteriophages and microbial interactions
- Biochemical effects in animals
- Glycosylation and Glycoproteins Research
- Stochastic processes and statistical mechanics
- Liquid Crystal Research Advancements
Harvard University
2016-2025
Harvard University Press
2005-2025
Google (United States)
2018
University of Chicago
2012
Ben-Gurion University of the Negev
2011
University of Lisbon
2010
Dana-Farber Cancer Institute
2009
University of Warwick
2008
University of Pennsylvania
2002-2008
University of Cambridge
2001-2005
The statistical mechanics of protein folding implies that the best-folding proteins are those have native conformation as a pronounced energy minimum. We show this can be obtained by proper selection sequences and suggest simple practical way to find these sequences. with optimized structure is discussed. These concepts tested lattice model full enumeration compact conformations. Selected shown state very stable kinetically accessible.
Class A G-protein-coupled receptors (GPCRs) influence virtually every aspect of human physiology. Understanding receptor activation mechanism is critical for discovering novel therapeutics since about one-third all marketed drugs target members this family. GPCR an allosteric process that couples agonist binding to G-protein recruitment, with the hallmark outward movement transmembrane helix 6 (TM6). However, what leads TM6 and key residue level changes remain less well understood. Here, we...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSpecific Nucleus as the Transition State for Protein Folding: Evidence from Lattice ModelV. I. Abkevich, A. M. Gutin, and E. ShakhnovichCite this: Biochemistry 1994, 33, 10026–10036Publication Date (Print):August 1, 1994Publication History Published online1 May 2002Published inissue 1 August 1994https://pubs.acs.org/doi/10.1021/bi00199a029https://doi.org/10.1021/bi00199a029research-articleACS PublicationsRequest reuse permissionsArticle...
It is shown that the kinetics of collapse a polymer coil consisting N segments after an abrupt decrease temperature two-stage process if >> Ne. The first stage takes time ∼ N2 and leads to peculiar state — crumpled, or fractal, globule. Any part chain any scale itself globule in this ; these parts are segregated from each other space due non-phantomness chain. fold crumpled fractal line with dimension 3, equal dimension. second knotting it realized by means reptation-like mechanism motion,...
The entropic component of the free energy assembly for multiparticle hydrogen-bonded aggregates is analyzed using a model based on balls connected by rigid rods or flexible strings. entropy assembly, ΔS, partitioned into translational, rotational, vibrational, and conformational components. While previously reported theoretical treatments rotational vibrational entropies are adequate, translational in solution entropyoften two largest components ΔSare not. This paper provides improved...
Multivalent biopolymers phase separate into membrane-less organelles (MLOs) which exhibit liquid-like behavior. Here, we explore formation of prototypical MOs from multivalent proteins on various time and length scales show that the kinetically arrested metastable multi-droplet state is a dynamic outcome interplay between two competing processes: diffusion-limited encounter proteins, exhaustion available valencies within smaller clusters. Clusters with satisfied cannot coalesce readily,...
The folding of many small proteins is kinetically a two-state process that represents overcoming the major free-energy barrier. A kinetic characteristic conformation, its probability to descend native state domain in amount time fraction total time, has been introduced determine which side barrier conformation belongs. However, features make protein on pathway become committed rapidly descending mystery. Using two small, well characterized proteins, CI2 and C-Src SH3, we show how topological...
Many attempts have been made to resolve in time the folding of model proteins computer simulations. Different computational approaches emerged. Some these suffer from insensitivity geometrical properties (lattice models), whereas others are computationally heavy (traditional molecular dynamics).We used recently proposed approach Zhou and Karplus study a protein based on discrete dynamics algorithm. We show that this algorithm resolves with respect <--> unfolding transition. In addition, we...
Results of Monte Carlo simulations folding a model ``protein,'' which is freely joined 27-monomer chain on simple cubic lattice with nearest-neighbor interactions, are reported. All compact self-avoiding conformations this have been enumerated, and the conformation (``native'') corresponding to global minimum energy known for each sequence. Only one out thirty sequences folds finds minimum. For sequence, process has two-stage character, rapid noncooperative compactization followed by slower...
We report a blind test of lattice-model-based search strategies for finding global minima model protein chains. One us (E.I.S.) selected 10 compact conformations 48-mer chains on the three-dimensional cubic lattice and used their inverse folding algorithm to design HP (H, hydrophobic; P, polar) sequences that should fold those "target" structures. The sequences, but not structures, were sent UCSF group (K.Y., K.M.F., P.D.T., H.S.C., K.A.D.), who two methods attempt find globally optimal...
There have been considerable attempts in the past to relate phenotypic trait—habitat temperature of organisms—to their genotypes, most importantly compositions genomes and proteomes. However, despite accumulation anecdotal evidence, an exact conclusive relationship between former latter has elusive. We present exhaustive study amino acid composition proteomes, nucleotide DNA, optimal growth (OGT) prokaryotes. Based on 204 complete proteomes archaea bacteria spanning range from −10 °C 110 °C,...
Analysis of structures and sequences several hyperthermostable proteins from various sources reveals two major physical mechanisms their thermostabilization. The first mechanism is “structure-based,” whereby some are significantly more compact than mesophilic homologues, while no particular interaction type appears to cause stabilization; rather, a sheer number interactions responsible for thermostability. Other employ an alternative, “sequence-based” thermal stabilization. They do not show...
Exhaustive enumeration of all compact self-avoiding conformations a chain 27 monomers on the 3*3*3 fragment simple cubic lattice is given. Total number unrelated by symmetry 103 346. This relatively small which makes it possible to make numerically exact calculation thermodynamic functions this chain. Heteropolymers with random sequence links were considered, and freezing transition at finite temperature was observed. analogous folding in proteins where unique structure formed. The numeric...
Journal Article A new approach to the design of stable proteins Get access E.I. Shakhnovich, Shakhnovich 1 Department Chemistry, Harvard University12 Oxford Street, Cambridge, MA 02138, USA 1To whom correspondence should be addressed Search for other works by this author on: Academic PubMed Google Scholar A.M. Gutin Protein Engineering, Design and Selection, Volume 6, Issue 8, November 1993, Pages 793–800, https://doi.org/10.1093/protein/6.8.793 Published: 01 1993 history Received: 20 March...
The size and origin of the protein fold universe is fundamental practical importance. Analyzing randomly generated, compact sticky homopolypeptide conformations constructed in generic simplified all-atom models, all have similar folds library solved structures, Protein Data Bank, conversely, compact, single-domain structures Bank structural analogues model set. Thus, both sets are highly likely complete, with arising from hydrogen-bonded, secondary structures. Because side chains represented...