Related papers: Physical principles of building protein megacomple…
Inside a cell, heterotypic proteins assemble in inhomogeneous, crowded systems where the abundance of these proteins vary with cell types. While some protein complexes form putative structures that can be visualized with imaging, there are…
In living cells, proteins self-assemble into large functional structures based on specific interactions between molecularly complex patches. Due to this complexity, protein self-assembly results from a competition between a large number of…
A statistical mechanical theory is presented to predict the effects of macromolecular crowding on protein association equilibria, accounting for both excluded volume and attractive interactions between proteins and crowding molecules.…
Cellular functions are established through biological evolution, but are constrained by the laws of physics. For instance, the physics of protein folding limits the lengths of cellular polypeptide chains. Consequently, many cellular…
Integrative modeling enables structure determination for large macromolecular assemblies by combining data from multiple sources of experiment data with theoretical and computational predictions. Recent advancements in AI-based structure…
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…
How do living cells achieve sufficient abundances of functional protein complexes while minimizing promiscuous non-functional interactions? Here we study this problem using a first-principle model of the cell whose phenotypic traits are…
Proteins and other macromolecules exist not in a single state but as dynamic ensembles of interconverting conformations, which are essential for catalysis, allosteric regulation, and molecular recognition. While AI-based structure…
Biomolecular condensates self-assemble when proteins and nucleic acids spontaneously demix to form droplets within the crowded intracellular milieu. This simple mechanism underlies the formation of a wide variety of membraneless…
The possibility for proteins to aggregate in different superstructures, i.e. large-scale polymorphism, has been widely observed, but an understanding of the physico-chemical mechanisms behind it is still out of reach. Here we present a…
Protein folding, peptide aggregation and crystallization, as well as adsorption of molecules on soft or solid substrates have an essential feature in common: In all these processes, structure formation is guided by a collective, cooperative…
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…
Proteins in organisms, rather than act alone, usually form protein complexes to perform cellular functions. We analyze the topological network structure of protein complexes and their component proteins in the budding yeast in terms of the…
The capacity of proteins to interact specifically with one another underlies our conceptual understanding of how living systems function. Systems-level study of specificity in protein-protein interactions is complicated by the fact that the…
Natural protein sequences that self-assemble to form globular structures are compact with high packing densities in the folded states. It is known that proteins unfold upon addition of denaturants, adopting random coil structures. The…
Intrinsically disordered proteins (IDPs) and multidomain proteins with flexible linkers show a high level of structural heterogeneity and are best described by ensembles consisting of multiple conformations with associated thermodynamic…
Protein dynamics in cells may be different from that in dilute solutions in vitro since the environment in cells is highly concentrated with other macromolecules. This volume exclusion due to macromolecular crowding is predicted to affect…
Generative modeling has become a central paradigm in protein research, extending machine learning beyond structure prediction toward sequence design, backbone generation, inverse folding, and biomolecular interaction modeling. However, the…
Circular permutation connects the N and C termini of a protein and concurrently cleaves elsewhere in the chain, providing an important mechanism for generating novel protein fold and functions. However, their in genomes is unknown because…
Complexes of physically interacting proteins are one of the fundamental functional units responsible for driving key biological mechanisms within the cell. Their identification is therefore necessary not only to understand complex formation…