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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…
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…
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…
Proteins populate a manifold in the high-dimensional sequence space whose geometrical structure guides their natural evolution. Leveraging recently-developed structure prediction tools based on transformer models, we first examine the…
Recently described stochastic models of protein evolution have demonstrated that the inclusion of structural information in addition to amino acid sequences leads to a more reliable estimation of evolutionary parameters. We present a…
Explainable and interpretable unsupervised machine learning helps understand the underlying structure of data. We introduce an ensemble analysis of machine learning models to consolidate their interpretation. Its application shows that…
Proteins are constructed from a limited alphabet of ~20 amino acids, yet the origins and selection of this specific alphabet are unresolved. One largely overlooked aspect is whether elemental composition constrains the range of viable…
We show that the holographic principle in quantum gravity imposes a strong constraint on life. The degrees of freedom of an organism can be estimated according to the theory of Boolean networks, which is constrained by the entropy bound.…
This paper investigates the dynamics of Ebola virus transmission in West Africa during 2014. The reproduction numbers for the total period of epidemic and for different consequent time intervals are estimated based on a newly suggested…
Stationary probability distributions of one-dimensional random walks on lattices with aperiodic disorder are investigated. The pattern of the distribution is closely related to the diffusional behavior, which depends on the wandering…
The genetic code is considered to be universal. In order to test if some statistical properties of the coding bacterial genome were due to inherent properties of the genetic code, we compared the autocorrelation function, the scaling…
Containing the recent West African outbreak of Ebola virus (EBOV) required the deployment of substantial global resources. Operationally, health workers and surveillance teams treated cases, collected genetic samples, and tracked case…
One of the most puzzling and unsolved challenges in molecular biology is understanding how proteins fold. Despite having advanced predictive tools that can accurately estimate the native structures of proteins, we still lack a comprehensive…
The immune system is a real-time example of an evolving system that navigates the essentially infinite complexity of protein sequence space. How this system responds to disease and vaccination is discussed. Of particular focus is the case…
The enormous size and complexity of genotypic sequence space frequently requires consideration of coarse-grained sequences in empirical models. We develop scaling relations to quantify the effect of this coarse-graining on properties of…
While all the information required for the folding of a protein is contained in its amino acid sequence, one has not yet learnt how to extract this information so as to predict the detailed, biological active, three-dimensional structure of…
Here we review the development of protein scaling theory, starting from backgrounds in mathematics and statistical mechanics, and leading to biomedical applications. Evolution has organized each protein family in different ways, but scaling…
The titled subject has attracted much interest. Here we summarize the substantial results obtained by a physical model of protein evolution based on hydropathic domain dynamics. In a recent Letter eighteen biologists suggested that the…
Cell type (e.g. pluripotent cell, fibroblast) is the end result of many complex processes that unfold due to evolutionary, developmental, and transformational stimuli. A cell's phenotype and the discrete, a priori states that define various…
Because of their large size and widespread mechanosensitive interactions the only recently discovered titled transmembrane proteins have attracted much attention. Here we present and discuss their hydropathic profiles using a new method of…