Related papers: Interrelationship Between Protein Electrostatics a…
Classical population genetics a priori assigns fitness to alleles without considering molecular or functional properties of proteins that these alleles encode. Here we study population dynamics in a model where fitness can be inferred from…
An important question in molecular evolution is whether an amino acid that occurs at a given position makes an independent contribution to fitness, or whether its effect depends on the state of other loci in the organism's genome, a…
Hydrogen bond networks play vital roles in biological functions ranging from protein folding to enzyme catalysis. Here we combine electronic structure calculations and ab initio path integral molecular dynamics simulations, which…
The probability-scale residual (PSR) is well defined across a wide variety of variable types and models, making it useful for studies of HIV/AIDS. In this manuscript, we highlight some of the properties of the PSR and illustrate its…
Electrostatic forces play many important roles in molecular biology, but are hard to model due to the complicated interactions between biomolecules and the surrounding solvent, a fluid composed of water and dissolved ions. Continuum model…
An exactly solvable model based on the topology of a protein native state is applied to identify bottlenecks and key-sites for the folding of HIV-1 Protease. The predicted sites are found to correlate well with clinical data on resistance…
We introduce a data-driven epistatic model of protein evolution, capable of generating evolutionary trajectories spanning very different time scales reaching from individual mutations to diverged homologs. Our in silico evolution…
The primary structure of proteins, that is their sequence, represents one of the most abundant set of experimental data concerning biomolecules. The study of correlations in families of co--evolving proteins by means of an inverse…
One of the main trend in to date research and development is the miniaturization of electronic devices. In this perspective, integrated nanodevices based on proteins or biomolecules are attracting a major interest. In fact, it has been…
We propose a model that explains the hierarchical organization of proteins in fold families. The model, which is based on the evolutionary selection of proteins by their native state stability, reproduces patterns of amino acids conserved…
The emergence of new variants of SARS-CoV-2 is a major concern given their potential impact on the transmissibility and pathogenicity of the virus as well as the efficacy of therapeutic interventions. Here, we predict the mutability of all…
In physics of living systems, a search for relationships of a few macroscopic variables that emerge from many microscopic elements is a central issue. We evolved gene regulatory networks so that the expression of target genes (partial…
We study the elastic response of a worm-like polymer chain with reversible kink-like structural defects. This is a generic model for (a) the double-stranded DNA with sharp bends induced by binding of certain proteins, and (b) effects of…
Phi-values are experimental measures of the effects of mutations on the folding kinetics of a protein. A central question is which structural information Phi-values contain about the transition state of folding. Traditionally, a Phi-value…
Energetically responsive residues of the 173 amino acid N-terminal domain of the cardiac Ryanodine receptor RyR2 are identified by a simple elastic net model. Residues that respond in a correlated way to fluctuations of spatially…
Atomic motions and energetics for a phosphate transfer reaction catalyzed by the cAMP-dependent protein kinase (PKA) are calculated by plane-wave density functional theory, starting from structures of proteins crystallized in both the…
The electrostatic contribution to twist rigidity of DNA is studied, and it is shown that the Coulomb self-energy of the double-helical sugar-phosphate backbone contributes considerably to twist rigidity of DNA--the electrostatic twist…
Protein sequence data from nature exhibits survivorship bias: we only observe data from those organisms that survive and reproduce, while non-functional protein mutations are eliminated by natural selection. Thus, predicting whether a…
Proteins play a central role in biology from immune recognition to brain activity. While major advances in machine learning have improved our ability to predict protein structure from sequence, determining protein function from structure…
Interacting proteins coevolve at multiple but interconnected scales, from the residue-residue over the protein-protein up to the family-family level. The recent accumulation of enormous amounts of sequence data allows for the development of…