Related papers: Stability of Designed Proteins Against Mutations

We use a three dimensional cubic lattice model of proteins to study their properties that determine folding to the native state. The protein chain is modeled as a sequence of $N$ beads. The interactions between beads are taken from a…

How robust is the natural genetic code with respect to mistranslation errors? It has long been known that the genetic code is very efficient in limiting the effect of point mutation. A misread codon will commonly code either for the same…

Assuming that mutation and fixation processes are reversible Markov processes, we prove that the equilibrium ensemble of sequences obeys a Boltzmann distribution with $\exp(4N_e m(1 - 1/(2N)))$, where $m$ is Malthusian fitness and $N_e$ and…

We propose a new and effective means for designing stable and fast-folding polypeptide sequences using a cumulant expansion of the molecular partition function. This method is unique in that $T_{Z}$, the ``cumulant design temperature''…

Structure-based protein design has attracted increasing interest, with numerous methods being introduced in recent years. However, a universally accepted method for evaluation has not been established, since the wet-lab validation can be…

Understanding the relationship between protein sequence, function, and stability is a fundamental problem in biology. While high-throughput methods have produced large numbers of sequence-function pairs, functional assays do not distinguish…

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…

The binding of a ligand molecule to a protein is often accompanied by conformational changes of the protein. A central question is whether the ligand induces the conformational change (induced-fit), or rather selects and stabilizes a…

Deep generative models that learn from the distribution of natural protein sequences and structures may enable the design of new proteins with valuable functions. While the majority of today's models focus on generating either sequences or…

The ability to computationally generate novel yet physically foldable protein structures could lead to new biological discoveries and new treatments targeting yet incurable diseases. Despite recent advances in protein structure prediction,…

The 21st century is presenting humankind with unprecedented environmental and medical challenges. The ability to design novel proteins tailored for specific purposes could transform our ability to respond timely to these issues. Recent…

Here we present an approximate analytical theory for the relationship between a protein structure's contact matrix and the shape of its energy spectrum in amino acid sequence space. We demonstrate a dependence of the number of sequences of…

In this paper we show that a dynamical description of the protein folding process provides an effective representation of equilibrium properties and it allows for a direct investigation of the mechanisms ruling the approach towards the…

Proteins are biological polymers that underlie all cellular functions. The first high-resolution protein structures were determined by x-ray crystallography in the 1960s. Since then, there has been continued interest in understanding and…

Deep learning has transformed protein design, enabling accurate structure prediction, sequence optimization, and de novo protein generation. Advances in single-chain protein structure prediction via AlphaFold2, RoseTTAFold, ESMFold, and…

Protein folding is the intricate process by which a linear sequence of amino acids self-assembles into a unique three-dimensional structure. Protein folding kinetics is the study of pathways and time-dependent mechanisms a protein undergoes…

Accurately determining a change in protein binding affinity upon mutations is important for the discovery and design of novel therapeutics and to assist mutagenesis studies. Determination of change in binding affinity upon mutations…

The prediction of the three-dimensional structures of the native state of proteins from the sequences of their amino acids is one of the most important challenges in molecular biology. An essential ingredient to solve this problem within…

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…

Recently described stochastic models of protein evolution have demonstrated that the inclusion of structural information in addition to amino acid sequences leads to a more reliable estimation of evolutionary parameters. We present a…