Related papers: Inferring repeat protein energetics from evolution…
The understanding, and even the description of protein folding is impeded by the complexity of the process. Much of this complexity can be described and understood by taking a statistical approach to the energetics of protein conformation,…
Protein sequences are believed to have been selected to provide the stability of, and reliable renaturation to, an encoded unique spatial fold. In recently proposed theoretical schemes, this selection is modeled as ``minimal frustration,''…
We show how to localize and quantify the functional evolutionary constraints on natural proteins. The method compares the perturbations caused by local sequence variants to the energetics of the protein folding process and to the…
Statistical analysis of alignments of large numbers of protein sequences has revealed "sectors" of collectively coevolving amino acids in several protein families. Here, we show that selection acting on any functional property of a protein,…
We carry out a theoretical study of the vibrational and relaxation properties of naturally-occurring proteins with the purpose of characterizing both the folding and equilibrium thermodynamics. By means of a suitable model we provide a full…
We propose an application of molecular information theory to analyze the folding of single domain proteins. We analyze results from various areas of protein science, such as sequence-based potentials, reduced amino acid alphabets, backbone…
We study the impact of mutations (changes in amino acid sequence) on the thermodynamics of simple protein-like heteropolymers consisting of N monomers, representing the amino acid sequence. The sequence is designed to fold into its native…
Biological forces govern essential cellular and molecular processes in all living organisms. Many cellular forces, e.g. those generated in cyclic conformational changes of biological machines, have repetitive components. However, little is…
Exploring and understanding the protein-folding problem has been a long-standing challenge in molecular biology. Here, using molecular dynamics simulation, we reveal how parallel distributed adjacent planar peptide groups of unfolded…
We study folding dynamics of protein-like sequences on square lattice using physical move set that exhausts all possible conformational changes. By analytically solving the master equation, we follow the time-dependent probabilities of…
Understanding the relationship between protein sequence, function, and stability is a fundamental problem in biology. While high-throughput methods have produced large numbers of sequence-function pairs, functional assays do not distinguish…
A protein's function depends critically on its conformational ensemble, a collection of energy weighted structures whose balance depends on temperature and environment. Though recent deep learning (DL) methods have substantially advanced…
While all the information required for the folding of a protein is contained in its amino acid sequence, one has not yet learned how to extract this information to predict the three--dimensional, biologically active, native conformation of…
A theoretical framework is developed to study the dynamics of protein folding. The key insight is that the search for the native protein conformation is influenced by the rate r at which external parameters, such as temperature, chemical…
We propose a general theory to describe the distribution of protein-folding transition paths. We show that transition paths follow a predictable sequence of high-free-energy transient states that are separated by free-energy barriers. Each…
Understanding the observed variability in the number of homologs of a gene is a very important, unsolved problem that has broad implications for research into co-evolution of structure and function, gene duplication, pseudogene formation…
Recent experimental results suggest that the native fold, or topology, plays a primary role in determining the structure of the transition state ensemble, at least for small fast folding proteins. To investigate the extent of the…
The sequence of a protein is not only constrained by its physical and biochemical properties under current selection, but also by features of its past evolutionary history. Understanding the extent and the form that these evolutionary…
The protein folding problem has attracted an increasing attention from physicists. The problem has a flavor of statistical mechanics, but possesses the most common feature of most biological problems -- the profound effects of evolution. I…
It has been conjectured that evolution exerted pressure to preserve amino acids bearing thermodynamic, kinetic, and functional roles. In this letter we show that the physical requirement to maintain protein stability gives rise to a…