Related papers: Topology, Geometry, and Stability: Protein Folding…
Proteins, by virtue of their central role in most biological processes, represent one of the key subjects of the study of molecular evolution. Inherent to the indispensability of proteins for living cells is the fact that a given protein…
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…
One of the most puzzling and unsolved challenges in molecular biology is understanding how proteins fold. Despite having advanced predictive tools that can accurately estimate the native structures of proteins, we still lack a comprehensive…
We present a statistical mechanics approach to the protein folding problem. We first review some of the basic properties of proteins, and introduce some physical models to describe their thermodynamics. These models rely on a random…
Novel numerical techniques, validated by an analysis of barnase and chymotrypsin inhibitor, are used to elucidate the paramount role played by the geometry of the protein backbone in steering the folding to the correct native state. It is…
Functional proteins must fold with some minimal stability to a structure that can perform a biochemical task. Here we use a simple model to investigate the relationship between the stability requirement and the capacity of a protein to…
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…
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…
Folding and aggregation of proteins, the interaction between proteins and membranes, as well as the adsorption of organic soft matter to inorganic solid substrates belong to the most interesting challenges in understanding structure and…
Recent experimental results suggest that the native fold, or topology, plays a primary role in determining the structure of the transition state ensemble, at least for small fast folding proteins. To investigate the extent of the…
We present an analysis of the effects of global topology on the structural stability of folded proteins in thermal equilibrium with a heat bath. For a large class of single domain proteins, we computed the harmonic spectrum within the…
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…
Neither of the two prevalent theories, namely thermodynamic stability and kinetic stability, provides a comprehensive understanding of protein folding. The thermodynamic theory is misleading because it assumes that free energy is the…
One of the classical questions in evolutionary biology is how evolutionary processes are coupled at the gene and species level. With this motivation, we compare the topological properties (mainly the depth scaling, as a characterization of…
In spite of decades of research, much remains to be discovered about folding: the detailed structure of the initial (unfolded) state, vestigial folding instructions remaining only in the unfolded state, the interaction of the molecule with…
We propose a model that explains the hierarchical organization of proteins in fold families. The model, which is based on the evolutionary selection of proteins by their native state stability, reproduces patterns of amino acids conserved…
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…
Proteins are a matter of dual nature. As a physical object, a protein molecule is a folded chain of amino acids with multifarious biochemistry. But it is also an instantiation along an evolutionary trajectory determined by the function…
The protein folding problem is stated and a list of properties that do not depend upon specific molecules is compiled and analyzed. The relationship of this analysis to future simulations is emphasized. The choice of power and time as…
Binding interactions between proteins and other molecules mediate numerous cellular processes, including metabolism, signaling, and regulation of gene expression. These interactions evolve in response to changes in the protein's chemical or…