Related papers: Designability and Thermal Stability of Protein Str…
The protein folding problem has attracted an increasing attention from physicists. The problem has a flavor of statistical mechanics, but possesses the most common feature of most biological problems -- the profound effects of evolution. I…
Protein structures are a very special class among all possible structures. It was suggested that a ``designability principle'' plays a crucial role in nature's selection of protein sequences and structures. Here we provide a theoretical…
Among an infinite number of possible folds, nature has chosen only about 1000 distinct folds to form protein structures. Theoretical studies suggest that selected folds are intrinsically more designable than others; these selected folds are…
Making use of a simplified model for protein folding, it can be shown that conformations which are particularly stable when their energy is minimized with respect to amino acid sequence (in the sense that they display a large energy gap to…
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…
Protein folds are highly designable, in the sense that many sequences fold to the same conformation. In the present work we derive an expression for the designability in a 20 letter lattice model of proteins which, relying only on the…
The stability of model proteins with designed sequences is assessed in terms of the number of sequences (obtained from the designed sequence through mutations), which fold into 5the ``native'' conformation. By a complete enumeration of the…
In the framework of a lattice-model study of protein folding, we investigate the interplay between designability, thermodynamic stability, and kinetics. To be ``protein-like'', heteropolymers must be thermodynamically stable, stable against…
Native protein folds often have a high degree of symmetry. We study the relationship between the symmetries of native proteins, and their designabilities -- how many different sequences encode a given native structure. Using a…
Lattice models, for their coarse-grained nature, are best suited for the study of the ``designability problem'', the phenomenon in which most of the about 16,000 proteins of known structure have their native conformations concentrated in a…
We review the recent progress in computational approaches to protein design which builds on advances in statistical-mechanical protein folding theory. In particular, we evaluate the degeneracy of the protein code (i.e. how many sequences…
A typical protein structure is a compact packing of connected alpha-helices and/or beta-strands. We have developed a method for generating the ensemble of compact structures a given set of helices and strands can form. The method is tested…
The aim of this work is to elucidate how physical principles of protein design are reflected in natural sequences that evolved in response to the thermal conditions of the environment. Using an exactly solvable lattice model, we design…
Despite the variety of protein sizes, shapes, and backbone configurations found in nature, the design of novel protein folds remains an open problem. Within simple lattice models it has been shown that all structures are not equally…
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…
Here we present an approximate analytical theory for the relationship between a protein structure's contact matrix and the shape of its energy spectrum in amino acid sequence space. We demonstrate a dependence of the number of sequences of…
In this work, we discovered a fundamental connection between selection for protein stability and emergence of preferred structures of proteins. Using standard exact 3-dimensional lattice model we evolve sequences starting from random ones…
Protein folding and design are major biophysical problems, the solution of which would lead to important applications especially in medicine. Here a novel protein model capable of simultaneously provide quantitative protein design and…
We propose a new and effective means for designing stable and fast-folding polypeptide sequences using a cumulant expansion of the molecular partition function. This method is unique in that $T_{Z}$, the ``cumulant design temperature''…
Using an off-lattice model, we fully enumerate folded conformations of polypeptide chains of up to N = 19 monomers. Structures are found to differ markedly in designability, defined as the number of sequences with that structure as a unique…