Related papers: Solution stability, neutral evolution and variabil…
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.…
A simple model of globular proteins which incorporates anisotropic attractions is proposed. It is closely related to models used to model simple hydrogen-bonding molecules such as water. Theories for both the fluid and solid phases are…
While all the information required for the folding of a protein is contained in its amino acid sequence, one has not yet learned how to extract this information to predict the three--dimensional, biologically active, native conformation of…
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…
Molecular phenotypes are important links between genomic information and organismic functions, fitness, and evolution. Complex phenotypes, which are also called quantitative traits, often depend on multiple genomic loci. Their evolution…
It is shown that a small subset of modes which are likely to be involved in protein functional motions of large amplitude can be determined by retaining the most robust normal modes obtained using different protein models. This result…
Comments: 6 pages RevTeX, 6 Postscript figures. We review a statistical mechanics treatment of the stability of globular proteins based on a simple model Hamiltonian taking into account protein self interactions and protein-water…
We introduce a new model of evolution on a fitness landscape possessing a tunable degree of neutrality. The model allows us to study the general properties of molecular species undergoing neutral evolution. We find that a number of…
The protein folding problem has attracted an increasing attention from physicists. The problem has a flavor of statistical mechanics, but possesses the most common feature of most biological problems -- the profound effects of evolution. I…
Proteins, essential to biological systems, perform functions intricately linked to their three-dimensional structures. Understanding the relationship between protein structures and their amino acid sequences remains a core challenge in…
Proteins are responsible for the most diverse set of functions in biology. The ability to extract information from protein sequences and to predict the effects of mutations is extremely valuable in many domains of biology and medicine.…
One of the main properties of biological systems is modularity, which manifests itself at all levels of their organization, starting with the level of molecular genetics, ending with the level of whole organisms and their communities. In a…
The structure and function of a protein are determined by its amino acid sequence. While random mutations change a protein's sequence, evolutionary forces shape its structural fold and biological activity. Studies have shown that neutral…
The theory of biochemical processes needs simple but realistic models of phenomena underlying microscopic dynamics of proteins. Many experiments performed in the 1980s have demonstrated that within the protein native state, apart from usual…
A growing number of experimental evidence shows that it is general for a ligand binding protein to have a potential for allosteric regulation and for further evolution. In addition, such proteins generically change their conformation upon…
The mutation and selection of regulatory DNA sequences is presented as an ideal model system of molecular evolution where genotype, phenotype, and fitness can be explicitly and independently characterized. In this theoretical study, we…
A Profile Mixture Model is a model of protein evolution, describing sequence data in which sites are assumed to follow many related substitution processes on a single evolutionary tree. The processes depend in part on different amino acid…
Molecular biology features numerous complexes of proteins that coordinate in an interlocking fashion to fulfill different functions. Adaptive evolution explains some of this complexity, but needn't be the default when neutral explanations…
Neutral landscapes and mutational robustness are believed to be important enablers of evolvability in biology. We apply these concepts to software, defining mutational robustness to be the fraction of random mutations that leave a program's…
In the course of evolution, proteins undergo important changes in their amino acid sequences, while their three-dimensional folded structure and their biological function remain remarkably conserved. Thanks to modern sequencing techniques,…