Related papers: Stability of Designed Proteins Against Mutations
Deep learning-based approaches, such as AlphaFold2 (AF2), have significantly advanced protein tertiary structure prediction, achieving results comparable to real biological experimental methods. While AF2 has shown limitations in predicting…
We estimate density of defects frozen into a biological Turing pattern which was turned on at a finite rate. A self-locking of gene expression in individual cells, which makes the Turing transition discontinuous, stabilizes the pattern…
Robustness to genetic or environmental disturbances is often considered as a key property of living systems. Yet, in spite of being discussed since the 1950s, how robustness emerges from the complexity of genetic architectures and how it…
We present the results of a self-consistent, unified molecular dynamics study of simple model heteropolymers in the continuum with emphasis on folding, sequence design and the determination of the interaction parameters of the effective…
Motivation Protein fold recognition is an important problem in structural bioinformatics. Almost all traditional fold recognition methods use sequence (homology) comparison to indirectly predict the fold of a tar get protein based on the…
We examined what determines the designability of 2-letter codes (H and P) lattice proteins from three points of view. First, whether the native structure is searched within all possible structures or within maximally compact structures.…
Understanding how monomeric proteins fold under in vitro conditions is crucial to describing their functions in the cellular context. Significant advances both in theory and experiments have resulted in a conceptual framework for describing…
Using the perturbation-response scanning (PRS) technique, we study a set of 23 proteins that display a variety of conformational motions upon ligand binding (e.g. shear, hinge, allosteric). In most cases, PRS determines residues that may be…
Proteins are macromolecules that mediate a significant fraction of the cellular processes that underlie life. An important task in bioengineering is designing proteins with specific 3D structures and chemical properties which enable…
We prove homological stability for sequences of "oriented configuration spaces" as the number of points in the configuration goes to infinity. These are spaces of configurations of n points in a connected manifold M of dimension at least 2…
Atomic packing is an important metric for characterizing protein structures, as it significantly influences various features including the stability, the rate of evolution and the functional roles of proteins. Packing in protein structures…
Evolution on neutral networks of genotypes has been found in models to concentrate on genotypes with high mutational robustness, to a degree determined by the topology of the network. Here analysis is generalized beyond neutral networks to…
Proteins are macromolecules that perform essential functions in all living organisms. Designing novel proteins with specific structures and desired functions has been a long-standing challenge in the field of bioengineering. Existing…
Protein one-dimensional (1D) structures such as secondary structure and contact number provide intuitive pictures to understand how the native three-dimensional (3D) structure of a protein is encoded in the amino acid sequence. However, it…
The human proteome is enriched in proteins that do not fold into a stable 3D structure. These intrinsically disordered proteins (IDPs) spontaneously fluctuate between a large number of configurations in their native form. Remarkably, the…
Generative artificial intelligence models learn probability distributions from data and produce novel samples that capture the salient properties of their training sets. Proteins are particularly attractive for such approaches given their…
An exactly solvable model based on the topology of a protein native state is applied to identify bottlenecks and key-sites for the folding of HIV-1 Protease. The predicted sites are found to correlate well with clinical data on resistance…
The structure and function of a protein are determined by its amino acid sequence. While random mutations change a protein's sequence, evolutionary forces shape its structural fold and biological activity. Studies have shown that neutral…
In this work we develop a microscopic physical model of early evolution, where phenotype,organism life expectancy, is directly related to genotype, the stability of its proteins in their native conformations which can be determined exactly…
We study the coupled dynamics of primary and secondary structure formation (i.e. slow genetic sequence selection and fast folding) in the context of a solvable microscopic model that includes both short-range steric forces and and…