Related papers: A new formulation of protein evolutionary models t…
Emergence of new protein structures has proved difficult to trace in nature and engineer in the laboratory. However, one aspect of structure evolution has proved immensely helpful for determining the three-dimensional structure of proteins…
The possibility of deriving the contact potentials between amino acids from their frequencies of occurence in proteins is discussed in evolutionary terms. This approach allows the use of traditional thermodynamics to describe such…
Biological diversity has evolved despite the essentially infinite complexity of protein sequence space. We present a hierarchical approach to the efficient searching of this space and quantify the evolutionary potential of our approach with…
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…
The observed correlations between pairs of homologous protein sequences are typically explained in terms of a Markovian dynamic of amino acid substitution. This model assumes that every location on the protein sequence has the same…
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…
Inverse protein folding is challenging due to its inherent one-to-many mapping characteristic, where numerous possible amino acid sequences can fold into a single, identical protein backbone. This task involves not only identifying viable…
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…
Understanding of the evolutionary origins of protein structures represents a key component of the understanding of molecular evolution as a whole. Here we seek to elucidate how the features of an underlying protein structural "space" might…
Protein-ligand interactions are one of the fundamental types of molecular interactions in living systems. Ligands are small molecules that interact with protein molecules at specific regions on their surfaces called binding sites. Tasks…
We derive an analytic expression for site-specific stationary distributions of amino acids from the Structurally Constrained Neutral (SCN) model of protein evolution with conservation of folding stability. The stationary distributions that…
In the protein sequence space, natural proteins form clusters of families which are characterized by their unique native folds whereas the great majority of random polypeptides are neither clustered nor foldable to unique structures. Since…
The structure of a protein is crucial in determining its functionality, and is much more conserved than sequence during evolution. A key task in structural biology is to compare protein structures in order to determine evolutionary…
Numerous cellular functions rely on protein$\unicode{x2013}$protein interactions. Efforts to comprehensively characterize them remain challenged however by the diversity of molecular recognition mechanisms employed within the proteome. Deep…
One of the most powerful techniques to study protein structures is to look for recurrent fragments (also called substructures or spatial motifs), then use them as patterns to characterize the proteins under study. An emergent trend consists…
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…
Motivation: Protein interactions are fundamental building blocks of biochemical reaction systems underlying cellular functions. The complexity and functionality of such systems emerge not from the protein interactions themselves but from…
Multiple sequence alignment (MSA) data play a crucial role in the study of protein mutations, with contact prediction being a notable application. Existing methods are often model-based or algorithmic and typically do not incorporate…
The intricate three-dimensional geometries of protein tertiary structures underlie protein function and emerge through a folding process from one-dimensional chains of amino acids. The exact spatial sequence and configuration of amino…
The biological functions of proteins often depend on dynamic structural ensembles. In this work, we develop a flow-based generative modeling approach for learning and sampling the conformational landscapes of proteins. We repurpose highly…