相关论文: The Energetics of Molecular Adaptation in Transcri…

Using the perturbation-response scanning (PRS) technique, we study a set of 23 proteins that display a variety of conformational motions upon ligand binding (e.g. shear, hinge, allosteric). In most cases, PRS determines residues that may be…

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…

A basic question of protein structural studies is to which extent mutations affect the stability. This question may be addressed starting from sequence and/or from structure. In proteomics and genomics studies prediction of protein…

Protein-DNA interactions are vital for many processes in living cells, especially transcriptional regulation and DNA modification. To further our understanding of these important processes on the microscopic level, it is necessary that…

Constraints on changes in expression levels across all cell components imposed by the steady growth of cells have recently been discussed both experimentally and theoretically. By assuming a small environmental perturbation and considering…

Proteins change their charge state through protonation and redox reactions as well as through binding charged ligands. The free energy of these reactions are dominated by solvation and electrostatic energies and modulated by protein…

Configurational entropy is an important factor in the free energy change of many macromolecular recognition and binding processes, and has been intensively studied. Despite great progresses that have been made, the global sampling remains…

Mutation rate is a key determinant of the pace as well as outcome of evolution, and variability in this rate has been shown in different scenarios to play a key role in evolutionary adaptation and resistance evolution under stress caused by…

A versatile approach to modeling the conformations and energetics of DNA loops is presented. The model is based on the classical theory of elasticity, modified to describe the intrinsic twist and curvature of DNA, the DNA bending…

The binding of a transcription factor (TF) to a DNA operator site can initiate or repress the expression of a gene. Computational prediction of sites recognized by a TF has traditionally relied upon knowledge of several cognate sites,…

The functions of proteins and RNAs are determined by a myriad of interactions between their constituent residues, but most quantitative models of how molecular phenotype depends on genotype must approximate this by simple additive effects.…

Evolution is a dynamic process. The two classical forces of evolution are mutation and selection. Assuming small mutation rates, evolution can be predicted based solely on the fitness differences between phenotypes. Predicting an…

The inheritance of characteristics induced by the environment has often been opposed to the theory of evolution by natural selection. Yet, while evolution by natural selection requires new heritable traits to be produced and transmitted, it…

The process of protein folding from an unfolded state to a biologically active, folded conformation is governed by many parameters e.g the sequence of amino acids, intermolecular interactions, the solvent, temperature and chaperon…

DNA loop formation is one of several mechanisms used by organisms to regulate genes. The free energy of forming a loop is an important factor in determining whether the associated gene is switched on or off. In this paper we use an elastic…

The perturbation of a transcription factor should affect the expression levels of its direct targets. However, not all genes showing changes in expression are direct targets. To increase the chance of detecting direct targets, we propose a…

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…

Predicting protein stability changes induced by single-point mutations has been a persistent challenge over the years, attracting immense interest from numerous researchers. The ability to precisely predict protein thermostability is…

Measuring natural selection on genomic elements involved in the cis-regulation of gene expression -- such as transcriptional enhancers and promoters -- is critical for understanding the evolution of genomes, yet it remains a major…

The free energy of looping DNA by proteins and protein complexes determines to what extent distal DNA sites can affect each other. We inferred its in vivo value through a combined computational-experimental approach for different lengths of…