Related papers: Stability of Designed Proteins Against Mutations
The aim of this work was to find a minimal set of structurally stable pentapeptides, which allows forming a polypeptide chain of a required 3D structure. To search for factors that ensure structural stability of the pentapeptide, we…
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…
While all the information required for the folding of a protein is contained in its amino acid sequence, one has not yet learnt how to extract this information so as to predict the detailed, biological active, three-dimensional structure of…
Deep generative models show promise for $\textit{de novo}$ protein design, yet reliably producing designs that are geometrically plausible, evolutionarily consistent, functionally relevant, and dynamically stable remains challenging. We…
The number of protein structures is far less than the number of sequences. By imposing simple generic features of proteins (low energy and compaction) on all possible sequences we show that the structure space is sparse compared to the…
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…
A simple lattice model for proteins that allows for distinct sizes of the amino acids is presented. The model is found to lead to a significant number of conformations that are the unique ground state of one or more sequences or encodable.…
By balancing the average energy gap with its typical change due to mutations for protein-like heteropolymers with M residues, we show that native states are unstable to mutations on a scale M* ~ (lambda/sigma_mu)^(1/zeta_s), where lambda is…
In structure-based models of proteins, one often assumes that folding is accomplished when all contacts are established. This assumption may frequently lead to a conceptual problem that folding takes place in a temperature region of very…
Inverse protein folding, the process of designing sequences that fold into a specific 3D structure, is crucial in bio-engineering and drug discovery. Traditional methods rely on experimentally resolved structures, but these cover only a…
In a similar way in which the folding of single--domain proteins provide an important test in the study of self--organization, the folding of homodimers constitute a basic challenge in the quest for the mechanisms which are at the basis of…
We simulate the evolution of model protein sequences subject to mutations. A mutation is considered neutral if it conserves 1) the structure of the ground state, 2) its thermodynamic stability and 3) its kinetic accessibility. All other…
It has been conjectured that evolution exerted pressure to preserve amino acids bearing thermodynamic, kinetic, and functional roles. In this letter we show that the physical requirement to maintain protein stability gives rise to a…
Genetic robustness, the preservation of evolved phenotypes against genotypic mutations, is one of the central concepts in evolution. In recent years a large body of work has focused on the origins, mechanisms, and consequences of robustness…
Lattice-model simulations and experiments of some small proteins suggest that folding is essentially controlled by a few conserved contacts. Residues of these conserved contacts form the minimum set of native contacts needed to ensure…
By exact computer enumeration and combinatorial methods, we have calculated the designability of proteins in a simple lattice H-P model for the protein folding problem. We show that if the strength of the non-additive part of the…
Deep learning approaches have produced substantial breakthroughs in fields such as image classification and natural language processing and are making rapid inroads in the area of protein design. Many generative models of proteins have been…
A general strategy is described for finding which amino acid sequences have native states in a desired conformation (inverse design). The approach is used to design sequences of 48 hydrophobic and polar aminoacids on three-dimensional…
Protein design has the potential to revolutionize biotechnology and medicine. While most efforts have focused on proteins with well-defined structures, increased recognition of the functional significance of intrinsically disordered…
We describe the results obtained from an improved model for protein folding. We find that a good agreement with the native structure of a 46 residue long, five-letter protein segment is obtained by carefully tuning the parameters of the…