相关论文: High fitness paths can connect proteins with low s…
The evolutionary trajectory of a protein through sequence space is constrained by function and three-dimensional (3D) structure. Residues in spatial proximity tend to co-evolve, yet attempts to invert the evolutionary record to identify…
We present a sequence-based probabilistic formalism that directly addresses co-operative effects in networks of interacting positions in proteins, providing significantly improved contact prediction, as well as accurate quantitative…
Determining the different conformational states of a protein and the transition paths between them is key to fully understanding the relationship between biomolecular structure and function. This can be accomplished by sampling protein…
How DNA is mapped to functional proteins is a basic question of living matter. We introduce and study a physical model of protein evolution which suggests a mechanical basis for this map. Many proteins rely on large-scale motion to…
Proteins populate a manifold in the high-dimensional sequence space whose geometrical structure guides their natural evolution. Leveraging recently-developed structure prediction tools based on transformer models, we first examine the…
The sequence of a protein is not only constrained by its physical and biochemical properties under current selection, but also by features of its past evolutionary history. Understanding the extent and the form that these evolutionary…
Mapping between sequence and structure is currently an open problem in structural biology. Despite many experimental and computational efforts it is not clear yet how the structure is encoded in the sequence. Answering this question may…
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…
Natural protein sequences somehow encode the structural forms that these molecules adopt. Recent developments in structure-prediction are agnostic to the mechanisms by which proteins fold and represent them as static objects. However, the…
Proteins evolve through complex sequence spaces, with fitness landscapes serving as a conceptual framework that links sequence to function. Fitness landscapes can be smooth, where multiple similarly accessible evolutionary paths are…
We develop a path-based approach to continuous-time random walks on networks with arbitrarily weighted edges. We describe an efficient numerical algorithm for calculating statistical properties of the stochastic path ensemble. After…
MOTIVATION: Proteins fold into complex structures that are crucial for their biological functions. Experimental determination of protein structures is costly and therefore limited to a small fraction of all known proteins. Hence, different…
Deep learning has been widely used for protein engineering. However, it is limited by the lack of sufficient experimental data to train an accurate model for predicting the functional fitness of high-order mutants. Here, we develop SESNet,…
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…
Inferring the structural properties of a protein from its amino acid sequence is a challenging yet important problem in biology. Structures are not known for the vast majority of protein sequences, but structure is critical for…
Geometric and structural constraints greatly restrict the selection of folds adapted by protein backbones, and yet, folded proteins show an astounding diversity in functionality. For structure to have any bearing on function, it is thus…
The analysis of the three-dimensional structure of proteins is an important topic in molecular biochemistry. Structure plays a critical role in defining the function of proteins and is more strongly conserved than amino acid sequence over…
Proteins are the basic building blocks of life. They usually perform functions by folding to a particular structure. Understanding the folding process could help the researchers to understand the functions of proteins and could also help to…
A protein structure is represented as a network of residues whereby edges are determined by intra-molecular contacts. We introduce inhomogeneity into these networks by assigning each edge a weight that is determined by amino-acid pair…
Natural genomes sometimes encode two different proteins in staggered reading frames of the same DNA sequence. Despite the prevalence of these 'overlapping genes' across the tree of life, it remains unknown whether arbitrary protein pairs…