Related papers: Sequence correlations shape protein promiscuity
In the course of evolution, proteins show a remarkable conservation of their three-dimensional structure and their biological function, leading to strong evolutionary constraints on the sequence variability between homologous proteins. Our…
Predicting compound-protein affinity is critical for accelerating drug discovery. Recent progress made by machine learning focuses on accuracy but leaves much to be desired for interpretability. Through molecular contacts underlying…
The 2024 Nobel Prize in Chemistry was awarded in part for protein structure prediction using AlphaFold2, an artificial intelligence/machine learning (AI/ML) model trained on vast amounts of sequence and 3D structure data. AlphaFold2 and…
Specific protein-protein interactions are crucial in the cell, both to ensure the formation and stability of multi-protein complexes, and to enable signal transduction in various pathways. Functional interactions between proteins result in…
Proteins must bind to specific other proteins in vivo in order to function. The proteins must bind only to one or a few other proteins of the of order a thousand proteins typically present in vivo. Using a simple model of a protein,…
Predicting three dimensional residue-residue contacts from evolutionary information in protein sequences was attempted already in the early 1990s. However, contact prediction accuracies of methods evaluated in CASP experiments before CASP11…
Studies of coevolution of amino acids within and between proteins have revealed two types of coevolving units: coevolving contacts, which are pairs of amino acids distant along the sequence but in contact in the three-dimensional structure,…
Several processes in the cell, such as gene regulation, start when key proteins recognise and bind to short DNA sequences. However, as these sequences can be hundreds of million times shorter than the genome, they are hard to find by simple…
Methods for alignment of protein sequences typically measure similarity by using substitution matrix with scores for all possible exchanges of one amino acid with another. Although widely used, the matrices derived from homologous sequence…
Atomic packing is an important metric for characterizing protein structures, as it significantly influences various features including the stability, the rate of evolution and the functional roles of proteins. Packing in protein structures…
Cooperativity plays an important role in the action of proteins bound to DNA. A simple, mechanical mechanism for cooperativity, in the form of a tension-mediated interaction between proteins bound to DNA at two different locations is…
Amino acid sequence portrays most intrinsic form of a protein and expresses primary structure of protein. The order of amino acids in a sequence enables a protein to acquire a particular stable conformation that is responsible for the…
The native conformation of structured proteins is stabilized by a complex network of interactions. We analyzed the elementary patterns that constitute such network and ranked them according to their importance in shaping protein sequence…
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 idea of this project is to study the protein structure and sequence relationship using the hidden markov model and artificial neural network. In this context we have assumed two hidden markov models. In first model we have taken protein…
Side chain flexibility is an important factor in ligand binding. In order to determine the extent to which side chain flexibility is involved in ligand binding, a knowledge-based approach was taken. A database composed of examples of…
Proteins are macromolecules that perform essential functions in all living organisms. Designing novel proteins with specific structures and desired functions has been a long-standing challenge in the field of bioengineering. Existing…
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.…
Genome-wide binding preferences of the key components of eukaryotic pre-initiation complex (PIC) have been recently measured with high resolution in Saccharomyces cerevisiae by Rhee and Pugh (Nature (2012) 483:295-301). Yet the rules…
Some natural proteins display recurrent structural patterns. Despite being highly similar at the tertiary structure level, repetitions within a single repeat protein can be extremely variable at the sequence level. We propose a mathematical…