Related papers: Prediction of site-specific amino acid distributio…
We review and further develop an analytical model that describes how thermodynamic constraints on the stability of the native state influence protein evolution in a site-specific manner. To this end, we represent both protein sequences and…
We simulate the evolution of a protein-like sequence subject to point mutations, imposing conservation of the ground state, thermodynamic stability and fast folding. Our model is aimed at describing neutral evolution of natural proteins. We…
The probability distribution of sequences with maximum entropy that satisfies a given amino acid composition at each site and a given pairwise amino acid frequency at each site pair is a Boltzmann distribution with $\exp(-\psi_N)$, where…
Neutral evolution is the simplest model of molecular evolution and thus it is most amenable to a comprehensive theoretical investigation. In this paper, we characterize the statistical properties of neutral evolution of proteins under the…
Recently described stochastic models of protein evolution have demonstrated that the inclusion of structural information in addition to amino acid sequences leads to a more reliable estimation of evolutionary parameters. We present a…
Natural protein sequences somehow encode the structural forms that these molecules adopt. Recent developments in structure-prediction are agnostic to the mechanisms by which proteins fold and represent them as static objects. However, the…
We present a sequence-based probabilistic formalism that directly addresses co-operative effects in networks of interacting positions in proteins, providing significantly improved contact prediction, as well as accurate quantitative…
Assuming that mutation and fixation processes are reversible Markov processes, we prove that the equilibrium ensemble of sequences obeys a Boltzmann distribution with $\exp(4N_e m(1 - 1/(2N)))$, where $m$ is Malthusian fitness and $N_e$ and…
Naturally evolving proteins gradually accumulate mutations while continuing to fold to thermodynamically stable native structures. This process of neutral protein evolution is an important mode of genetic change, and forms the basis for the…
Despite the importance of a thermodynamically stable structure with a conserved fold for protein function, almost all evolutionary models neglect site-site correlations that arise from physical interactions between neighboring amino acid…
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…
Protein sequences serve as a natural record of the evolutionary constraints that shape their functional structures. We show that it is possible to use only sequence information to go beyond predicting native structures and global stability…
A central goal of protein-folding theory is to predict the stochastic dynamics of transition paths --- the rare trajectories that transit between the folded and unfolded ensembles --- using only thermodynamic information, such as a…
The sensitivity of the native states of protein-like heteropolymers to mutations modelled as perturbations in the interaction potential between amino acids is studied. The stability threshold against mutations is shown to be zero for random…
Protein structure prediction has reached revolutionary levels of accuracy on single structures, yet distributional modeling paradigms are needed to capture the conformational ensembles and flexibility that underlie biological function.…
The accurate prediction of changes in protein stability under multiple amino acid substitutions is essential for realising true in-silico protein re-design. To this purpose, we propose improvements to state-of-the-art Deep learning (DL)…
Many crucial biological processes rely on networks of protein-protein interactions. Predicting the effect of amino acid mutations on protein-protein binding is vital in protein engineering and therapeutic discovery. However, the scarcity of…
Predicting the impact of single-point amino acid mutations on protein stability is essential for understanding disease mechanisms and advancing drug development. Protein stability, quantified by changes in Gibbs free energy ($\Delta\Delta…
Proteins have evolved through mutations, amino acid substitutions, since life appeared on Earth, some 109 years ago. The study of these phenomena has been of particular significance because of their impact on protein stability, function,…
Thermostability is an important prerequisite for enzymes employed for industrial applications. Several machine learning based models have thus been formulated for protein classification based on this particular trait. These models have…