Related papers: About the Protein Space Vastness
Generative machine learning models are increasingly being used to design novel proteins for therapeutic and biotechnological applications. However, the current methods mostly focus on the design of proteins with a fixed backbone structure,…
Proteins are biological polymers that underlie all cellular functions. The first high-resolution protein structures were determined by x-ray crystallography in the 1960s. Since then, there has been continued interest in understanding and…
Natively unfolded proteins exist as an ensemble of flexible conformations lacking a well defined tertiary structure along a large portion of their polypeptide chain. Despite the absence of a stable configuration, they are involved in…
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…
We show how to localize and quantify the functional evolutionary constraints on natural proteins. The method compares the perturbations caused by local sequence variants to the energetics of the protein folding process and to the…
In evolutionary dynamics, a key measure of a mutant trait's success is the probability that it takes over the population given some initial mutant-appearance distribution. This "fixation probability" is difficult to compute in general, as…
The tempo and mode of an adaptive process is strongly determined by the structure of the fitness landscape that underlies it. In order to be able to predict evolutionary outcomes (even on the short term), we must know more about the nature…
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…
Measures of biodiversity change such as the Living Planet Index describe proportional change in the abundance of a typical species, which can be thought of as change in the size of a community. Here, I discuss the orthogonal concept of…
Asymmetric segregation of key proteins at cell division -- be it a beneficial or deleterious protein -- is ubiquitous in unicellular organisms and often considered as an evolved trait to increase fitness in a stressed environment. Here, we…
The fractal properties of the total potential energy V as a function of time t are studied for a number of systems, including realistic models of proteins (PPT, BPTI and myoglobin). The fractal dimension of V(t), characterized by the…
Evolutionary computation offers a variety of tools to solve complex real-world optimization problems. However, research often focuses on smaller, simplified problems and optimization algorithms that sometimes miss expectations in real-world…
The characterization of plasticity, robustness, and evolvability, an important issue in biology, is studied in terms of phenotypic fluctuations. By numerically evolving gene regulatory networks, the proportionality between the phenotypic…
Chemical space which encompasses all stable compounds is unfathomably large and its dimension scales linearly with the number of atoms considered. The success of machine learning methods suggests that many physical quantities exhibit…
Classification of proteins based on their structure provides a valuable resource for studying protein structure, function and evolutionary relationships. With the rapidly increasing number of known protein structures, manual and…
In protein engineering, while computational models are increasingly used to predict mutation effects, their evaluations primarily rely on high-throughput deep mutational scanning (DMS) experiments that use surrogate readouts, which may not…
Activated processes such as protein unfolding are highly sensitive to heterogeneity in the environment. We study a highly simplified model of a protein in a random heterogeneous environment, a model of the in vivo environment. It is found…
Current-day genomes bear the mark of the evolutionary processes. One of the strongest indications is the sequence homology among families of proteins that perform similar biological functions in different species. The number of proteins in…
Gene expression is significantly stochastic making modeling of genetic networks challenging. We present an approximation that allows the calculation of not only the mean and variance but also the distribution of protein numbers. We assume…
Proteins, essential to biological systems, perform functions intricately linked to their three-dimensional structures. Understanding the relationship between protein structures and their amino acid sequences remains a core challenge in…