Related papers: Stability and the Evolvability of Function in a Mo…
Robustness is often regarded as a critical future challenge for real-world applications, where stability is essential. However, as models often learn tasks in a similar order, we hypothesize that easier tasks will be easier regardless of…
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…
We propose a protein model based on a hierarchy of constraints that force the protein to follow certain pathways when changing conformation. The model exhibits a first order phase transition, cooperativity and is exactly solvable. It also…
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…
We adopt the point of view that analysis of the stability of the protein folding process is central to understanding the underlying physics of folding. Stability of the folding process means that many perturbations do not disrupt the…
Proteins fold using a two-state or multi-state kinetic mechanisms, but up to now there isn't a first-principle model to explain this different behaviour. We exploit the network properties of protein structures by introducing novel…
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…
Understanding the protein folding process is an outstanding issue in biophysics; recent developments in molecular dynamics simulation have provided insights into this phenomenon. However, the large freedom of atomic motion hinders the…
Monte Carlo simulations of a simple lattice model of protein folding show two distinct regimes depending on the chain length. The first regime well describes the folding of small protein sequences and its kinetic counterpart appears to be…
In allosteric proteins, binding a ligand can affect function at a distant location, for example by changing the binding affinity of a substrate at the active site. The induced fit and population shift models, which differ by the assumed…
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…
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…
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…
The mutation and selection of regulatory DNA sequences is presented as an ideal model system of molecular evolution where genotype, phenotype, and fitness can be explicitly and independently characterized. In this theoretical study, we…
Protein structures in nature often exhibit a high degree of regularity (secondary structures, tertiary symmetries, etc.) absent in random compact conformations. We demonstrate in a simple lattice model of protein folding that structural…
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…
We carry out a theoretical study of the vibrational and relaxation properties of naturally-occurring proteins with the purpose of characterizing both the folding and equilibrium thermodynamics. By means of a suitable model we provide a full…
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…
The thermodynamics of proteins indicate that folding/unfolding takes place either through stable intermediates or through a two-state process without intermediates. The rather short folding times of the two-state process indicate that…
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…