Related papers: Stability of Designed Proteins Against Mutations
The native structures of proteins, except for notable exceptions of intrinsically disordered proteins, in general take their most stable conformation in the physiological condition to maintain their structural framework so that their…
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…
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…
We study the impact of mutations (changes in amino acid sequence) on the thermodynamics of simple protein-like heteropolymers consisting of N monomers, representing the amino acid sequence. The sequence is designed to fold into its native…
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…
Natural protein sequences contain a record of their history. A common constraint in a given protein family is the ability to fold to specific structures, and it has been shown possible to infer the main native ensemble by analyzing…
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…
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…
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…
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…
It is well known amongst molecular biologists that proteins with a common ancestor and that perform the same function in similar organisms, can have rather different amino-acid sequences. Mutations have altered the amino-acid sequences…
Discerning how a mutation affects the stability of a protein is central to the study of a wide range of diseases. Machine learning and statistical analysis techniques can inform how to allocate limited resources to the considerable time and…
While all the information required for the folding of a protein is contained in its amino acid sequence, one has not yet learned how to extract this information to predict the three--dimensional, biologically active, native conformation of…
Feature extraction is an unavoidable task, especially in the critical step of preprocessing biological sequences. This step consists for example in transforming the biological sequences into vectors of motifs where each motif is a…
The protein folding problem must ultimately be solved on all length scales from the atomic up through a hierarchy of complicated structures. By analyzing the stability of the folding process using physics and mathematics, this paper shows…
Mapping between sequence and structure is currently an open problem in structural biology. Despite many experimental and computational efforts it is not clear yet how the structure is encoded in the sequence. Answering this question may…
In order to extend the results obtained with minimal lattice models to more realistic systems, we study a model where proteins are described as a chain of 20 kinds of structureless amino acids moving in a continuum space and interacting…
Stabilizing proteins is a foundational step in protein engineering. However, the evolutionary pressure of all extant proteins makes identifying the scarce number of mutations that will improve thermodynamic stability challenging. Deep…
We seek to understand the interplay between amino acid sequence and local structure in proteins. Are some amino acids unique in their ability to fit harmoniously into certain local structures? What is the role of sequence in sculpting the…
The common understanding of protein evolution has been that neutral or slightly deleterious mutations are fixed by random drift, and evolutionary rate is determined primarily by the proportion of neutral mutations. However, recent studies…