The Dynamic Search Fireworks Algorithm (dynFWA) is an effective algorithm for solving optimization problems. However, dynFWA easily falls into local optimal solutions prematurely and it also has a slow convergence rate. In order to improve these prob...
We study the structure of the rest points of signaling games and their dynamic behavior under selection-mutation dynamics by taking the case of three signals as our canonical example. Many rest points of the replicator dynamics of signaling games are...
To strengthen the population diversity and search capability of equilibrium optimizer (EO), a dynamic multi-population mutation architecture-based equilibrium optimizer (DMMAEO) is proposed. Firstly, a dynamic multi-population guidance mechanism is c...
The deterministic framework of mutation semigroups provides algebraic conditions for evolutionary collapse, but real mutation processes are inherently stochastic. This paper develops a comprehensive theory of stochastic mutation semigroups, where ele...
Aiming at the issues of population diversity attenuation, insufficient search efficiency, and susceptibility to a local optimum in the equilibrium optimizer (EO), a dynamic heterogeneous search-mutation structure-based equilibrium optimizer (DHSMEO)...
When urban rail transit is affected by interference, the fluctuation pattern of passenger flow undergoes mutation, which is not conducive to its operational safety and sustainable development. The more intense the mutation in the passenger flow, the...
G12 mutations heavily affect conformational transformation and activity of KRAS. In this study, Gaussian accelerated molecular dynamics (GaMD) simulations were performed on the GDP-bound wild-type (WT), G12A, G12D, and G12R KRAS to probe mutation-med...
The salp swarm algorithm imitates the swarm behavior of salps during navigation and hunting that has been proven the superiority of search for best solution. However, although it has sufficient global search ability, it is still worth paying attentio...
Originating from the Luria–Delbrück experiment in 1943, fluctuation analysis (FA) has been well developed to demonstrate random mutagenesis in microbial cell populations and infer mutation rates. Despite the remarkable progress in its theo...
In this study, we combined all-atom MD simulations, the ensemble-based mutational scanning of protein stability and binding, and perturbation-based network profiling of allosteric interactions in the SARS-CoV-2 spike complexes with a panel of cross-r...
Ras proteins, as small GTPases, mediate cell proliferation, survival and differentiation. Ras mutations have been associated with a broad spectrum of human cancers and thus targeting Ras represents a potential way forward for cancer therapy. A recent...
Aiming at the problem of reduced positioning accuracy of unmanned swarm navigation systems due to dynamic abrupt noise in a complex electromagnetic environment, this paper proposes an adaptive Kalman filtering positioning and calibration method based...
Down regulation of the major histocompatibility class (MHC) I pathway plays an important role in tumour development, and can be achieved by suppression of HLA expression or mutations in the MHC peptide-binding pocket. The peptide-loading complex (PLC...
Structural and functional studies of the SARS-CoV-2 spike proteins have recently determined distinct functional states of the B.1.1.7 and B.1.351 spike variants, providing a molecular framework for understanding the mechanisms that link the effect of...
Tobacco etch virus protease (TEVp) is wildly exploited for various biotechnological applications. These applications take advantage of TEVp’s ability to cleave specific substrate sequences to study protein function and interactions. A major lim...
The ability of enzymes to recognize and process structurally diverse substrates is fundamental to metabolic flexibility and biological regulation. In melanin biosynthesis, human tyrosinase (Tyr) catalyzes the oxidation of several chemically distinct...
The adenomas in Cushing’s disease frequently exhibit mutations in exon 14, within a binding motif for the regulatory protein 14-3-3 located between the catalytic domain (DUB), responsible for ubiquitin hydrolysis, and the WW-like domain that me...
In humans and other eukaryotes, DNA is condensed into chromatin fibers that are further wound into chromosomes. This organization allows regulatory elements in the genome, often distant from each other in the linear DNA, to interact and facilitate ge...
In the growing field of biomolecular electronics, blue-copper Azurin stands out as one of the most widely studied protein in single-molecule contacts. Interestingly, despite the paramount importance of the structure/dynamics of molecular contacts in...
β-lactamases are enzymes produced by bacteria to hydrolyze β-lactam antibiotics as a common mechanism of resistance. Evolution in such enzymes has been rendering a wide variety of antibiotics impotent, therefore posing a major threat. Clini...
We introduce two new search strategies to further improve the performance of vegetation evolution (VEGE) for solving continuous optimization problems. Specifically, the first strategy, named the dynamic maturity strategy, allows individuals with bett...
The membrane Fo factor of ATP synthase is highly sensitive to mutations in the proton half-channel leading to the functional blocking of the entire protein. To identify functionally important amino acids for the proton transport, we performed molecul...
Postaxial Polydactyly (PAP) is a congenital disorder of limb abnormalities characterized by posterior extra digits. Mutations in the N-terminal region of the Zinc finger protein 141 (ZNF141) gene were recently linked with PAP type A. Zinc finger prot...
While drug resistance mutations can often be attributed to the loss of direct or solvent-mediated protein−ligand interactions in the drug-mutant complex, in this study we show that a resistance mutation for the picomolar HIV-1 capsid (CA)-targeting a...
GABA transporter 1 (GAT1), encoded by the SLC6A1 gene, is essential for maintaining inhibitory neurotransmission by mediating the reuptake of GABA from the synaptic cleft. Dysfunction of GAT1 has been linked to several neurological and neurodevelopme...
Background/Objectives: Antibody-dependent cellular cytotoxicity relies on the interaction between the Fc region of immunoglobulin G1 (IgG1) and the CD16a receptor. While removal of core fucosylation on Fc and introduction of the DFTE mutation set (S2...
Norovirus is a major cause of acute viral gastroenteritis in humans. Molecular biology-based detection methods play a pivotal role in ensuring accurate and specific diagnosis. The inclusion of Qβ phage particles as armored positive controls in t...
In this paper, a multi-strategy fusion enhanced Honey Badger algorithm (EHBA) is proposed to address the problem of easy convergence to local optima and difficulty in achieving fast convergence in the Honey Badger algorithm (HBA). The adoption of a d...
The inactivation of thrombin by antithrombin is highly enhanced by the presence of heparin chains forming “bridges” between the two proteins. X-ray structures for such ternary complexes have been published, but the molecular background of...
The ongoing pandemic caused by SARS-CoV-2 has gone through various phases. Since the initial outbreak, the virus has mutated several times, with some lineages showing even stronger infectivity and faster spread than the original virus. Among all the...
Human ileal bile acid-binding protein (hI-BABP) has a key role in the enterohepatic circulation of bile salts. Its two internal binding sites exhibit positive cooperativity accompanied by a site-selectivity of glycocholate (GCA) and glycochenodeoxych...
Since 1991, several genetic disorders caused by unstable trinucleotide repeats (TNRs) have been identified, collectively referred to as triplet repeat diseases (TREDs). They share a common mutation mechanism: the expansion of repeats (dynamic mutatio...
30 January 2022
Tuberculosis (TB), the most frequent bacterium-mediated infectious disease caused by Mycobacterium tuberculosis, has been known to infect humans since ancient times. Although TB is common worldwide, the most recent report by the WHO (World Health Org...
The most recent wave of SARS-CoV-2 Omicron variants descending from BA.2 and BA.2.86 exhibited improved viral growth and fitness due to convergent evolution of functional hotspots. These hotspots operate in tandem to optimize both receptor binding fo...
Mutations in genes encoding molecular chaperones, for instance the genes encoding the subunits of the chaperonin CCT (chaperonin containing TCP-1, also known as TRiC), are associated with rare neurodegenerative disorders. Using a classical molecular...
Under constant selection, each trait has a fixed fitness, and small mutation rates allow populations to efficiently exploit the optimal trait. Therefore, it is reasonable to expect that mutation rates will evolve downwards. However, we find that this...
Cancer is the second leading cause of death worldwide. The etiology of the disease has remained elusive, but mutations causing aberrant RNA splicing have been considered one of the significant factors in various cancer types. The association of aberr...
The conformational changes in switch domains significantly affect the activity of NRAS. Gaussian-accelerated molecular dynamics (GaMD) simulations of three separate replicas were performed to decipher the effects of G13D, Q16R, and C118S on the confo...
Tuberculosis (TB), caused by the Mycobacterium tuberculosis infection, continues to be a leading cause of morbidity and mortality in developing countries. Resistance to the first-line anti-TB drugs, isoniazid (INH) and rifampicin (RIF), is a major dr...
The fibroblast growth factor receptor 2 (FGFR2) gene is one of the most extensively studied genes with many known mutations implicated in several human disorders, including oncogenic ones. Most FGFR2 disease-associated gene mutations are missense mut...
The arithmetic optimization algorithm (AOA) is a new metaheuristic algorithm inspired by arithmetic operators (addition, subtraction, multiplication, and division) to solve arithmetic problems. The algorithm is characterized by simple principles, few...
The conformational heterogeneity of the p53 tumor suppressor, the wild-type (p53wt) and mutated forms, was investigated by a computational approach, including the modeling and all atoms of the molecular dynamics (MD) simulations. Four different punct...
Monogenic disorders present a compelling target for drug discovery due to their clear, single-gene etiology. Yet, effective therapies remain scarce, largely because diverse mutation types scattered across a protein obstruct targeted drug design. In t...
Smith-Lemli-Opitz syndrome (SLOS) is a cholesterol synthesis disorder characterized by physical, mental, and behavioral symptoms. It is caused by mutations in 7-dehydroxycholesterolreductase gene (DHCR7) encoding DHCR7 protein, which is the rate-limi...
Feline panleukopenia virus (FPV), a globally pervasive and highly pathogenic pathogen, has garnered significant attention recently due to the cross-species transmission of its variants. Despite the vast body of research conducted on FPV, studies expl...
Familial amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the selective degeneration of motor neurons. Among the main genetic causes of ALS, over 200 mutations have been identified in the Cu/Zn superoxid...
Congenital nephrogenic diabetes insipidus (CNDI) is a genetic disorder caused by mutations in arginine vasopressin receptor 2 (AVPR2) or aquaporin 2 genes, rendering collecting duct cells insensitive to the peptide hormone arginine vasopressin stimul...
(1) Background: Mutations in NFκB1, a transcriptional regulator of immunomodulating proteins, are a known cause of inborn errors of immunity. Our proband is a 22-year-old male with a diagnosis of common variable immunodeficiency (CVID), cytopen...
Peroxisome proliferator-activated receptors (PPARα, PPARβ/δ, and PPARγ) are ligand-regulated nuclear receptors that coordinate lipid metabolism, glucose homeostasis, inflammation, adipogenesis, differentiation, and disease-asso...
The ongoing COVID-19 pandemic follows an unpredictable evolution, driven by both host-related factors such as mobility, vaccination status, and comorbidities and by pathogen-related ones. The pathogenicity of its causative agent, SARS-CoV-2 virus, re...
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