Related papers: Selective Constraints on Amino Acids Estimated by …
Modern biomedicine is challenged to predict the effects of genetic variation. Systematic functional assays of point mutants of proteins have provided valuable empirical information, but vast regions of sequence space remain unexplored.…
We apply Markov chain lumping techniques to aggregate codons from an empirical substitution matrix. The standard genetic code as well as higher order amino acid substitution groups are identified. Since the aggregates are derived from first…
Evolutionary models measure the probability of amino acid substitutions occurring over different evolutionary distances. We examine various evolutionary models based on empirically derived amino acid substitution matrices. The models are…
Quantifying the effects of amino acid mutations in proteins presents a significant challenge due to the vast combinations of residue sites and amino acid types, making experimental approaches costly and time-consuming. The Potts model has…
Models of codon evolution are commonly used to identify positive selection. Positive selection is typically a heterogeneous process, i.e., it acts on some branches of the evolutionary tree and not others. Previous work on DNA models showed…
Statistical models for families of evolutionary related proteins have recently gained interest: in particular pairwise Potts models, as those inferred by the Direct-Coupling Analysis, have been able to extract information about the…
It is important to understand how protein folding and evolution influences each other. Several studies based on entropy calculation correlating experimental measurement of residue participation in folding nucleus and sequence conservation…
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…
Generating protein sequences conditioned on protein structures is an impactful technique for protein engineering. When synthesizing engineered proteins, they are commonly translated into DNA and expressed in an organism such as yeast. One…
Co-optimizing mRNA sequences for both codon optimality and secondary structure is crucial for producing stable and efficacious mRNA therapeutics. Codon optimization, which adjusts nucleotide sequences to enhance translational efficiency,…
The native structures of proteins, except for notable exceptions of intrinsically disordered proteins, in general take their most stable conformation in the physiological condition to maintain their structural framework so that their…
Cancer is a heterogeneous disease with different combinations of genetic and epigenetic alterations driving the development of cancer in different individuals. While these alterations are believed to converge on genes in key cellular…
Selection pressures on proteins are usually measured by comparing homologous nucleotide sequences (Zuckerkandl and Pauling 1965). Recently we introduced a novel method, termed `volatility', to estimate selection pressures on protein…
The persistence of life requires populations to adapt at a rate commensurate with the dynamics of their environment. Successful populations that inhabit highly variable environments have evolved mechanisms to increase the likelihood of…
The simplest approximation of interaction potential between amino-acids in proteins is the contact potential, which defines the effective free energy of a protein conformation by a set of amino acid contacts formed in this conformation.…
We propose a novel method for the determination of the effective interaction potential between the amino acids of a protein. The strategy is based on the combination of a new optimization procedure and a geometrical argument, which also…
Scientific practice typically involves repeatedly studying a system, each time trying to unravel a different perspective. In each study, the scientist may take measurements under different experimental conditions (interventions,…
Predicting the effect of mutations in proteins is one of the most critical challenges in protein engineering; by knowing the effect a substitution of one (or several) residues in the protein's sequence has on its overall properties, could…
Natural protein sequences contain a record of their history. A common constraint in a given protein family is the ability to fold to specific structures, and it has been shown possible to infer the main native ensemble by analyzing…
Under certain conditions, the dynamics of coarse-grained models of solvated proteins can be described using a Markov state model, which tracks the evolution of populations of configurations. The transition rates among states that appear in…