Several recently developed high-throughput techniques have changed the field of molecular virology. For example, proteomics studies reveal complete interactomes of a viral protein, genome-wide CRISPR knockout and activation screens probe the importan...
Sequence–function relationship in a protein is commonly determined by the three-dimensional protein structure followed by various biochemical experiments. However, with the explosive increase in the number of genome sequences, facilitated by recent...
The major concern with COVID-19 therapeutic monoclonal antibodies is the loss of efficacy against continuously emerging variants of SARS-CoV-2. To predict antibody efficacy against future Omicron subvariants, we conducted deep mutational scanning (DM...
Mutations may cause changes in the structure and function of immune-related proteins, thereby affecting the operation of the immune system. Deep mutational scanning combines saturation mutagenesis, functional selection, and high-throughput sequencing...
The rapid evolution of SARS-CoV-2 has led to the emergence of variants with increased immune evasion capabilities, posing significant challenges to antibody-based therapeutics and vaccines. In this study, we conducted a comprehensive structural and e...
The Zika virus has recently been shown to be associated with severe birth defects. The virus’ envelope (E) protein mediates its ability to infect cells and is also the primary target of the antibodies that are elicited by natural infection and...
Drug resistance is a major healthcare challenge, resulting in a continuous need to develop new inhibitors. The development of these inhibitors requires an understanding of the mechanisms of resistance for a critical mass of occurrences. Recent genome...
Identifying drug resistance mutations is important for the clinical use of antivirals and can help define both a drug’s mechanism of action and the mechanistic basis of resistance. Resistance mutations are often identified one-at-a-time by stud...
In this study, we performed a computational study of binding mechanisms for the SARS-CoV-2 spike Omicron XBB lineages with the host cell receptor ACE2 and a panel of diverse class one antibodies. The central objective of this investigation was to exa...
Although Rhesus macaques are an important animal model for HIV-1 vaccine development research, most transmitted HIV-1 strains replicate poorly in macaque cells. A major genetic determinant of this species-specific restriction is a non-synonymous muta...
For patients with colorectal cancer liver metastases (CRLM), the genetic mutation status is important in treatment selection and prognostication for survival outcomes. This study aims to investigate the relationship between radiomics imaging features...
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...
Mastering selective molecule trafficking across human cell membranes poses a formidable challenge in healthcare biotechnology while offering the prospect of breakthroughs in drug delivery, gene therapy, and diagnostic imaging. The cholera toxin B-sub...
In this study, we combine all-atom MD simulations and comprehensive mutational scanning of S-RBD complexes with the angiotensin-converting enzyme 2 (ACE2) host receptor in the native form as well as the S-RBD Delta and Omicron variants to (a) examine...
In this study, we performed all-atom MD simulations of RBD–ACE2 complexes for BA.1, BA.1.1, BA.2, and BA.3 Omicron subvariants, conducted a systematic mutational scanning of the RBD–ACE2 binding interfaces and analysis of electrostatic ef...
Viral resistance is a worldwide problem mitigating the effectiveness of antiviral drugs. Mutations in the drug-targeting proteins are the primary mechanism for the emergence of drug resistance. It is essential to identify the drug resistance mutation...
Evolutionary and functional studies have suggested that the emergence of Omicron variants can be determined by multiple fitness tradeoffs including immune escape, binding affinity, conformational plasticity, protein stability, and allosteric modulati...
The rapid evolution of SARS-CoV-2 has underscored the need for a detailed understanding of antibody binding mechanisms to combat immune evasion by emerging variants. In this study, we investigated the interactions between Class I neutralizing antibod...
About half of the mutations that lead to hypertrophic cardiomyopathy (HCM) occur in the MYBPC3 gene. However, the molecular mechanisms of pathogenicity of point mutations in cardiac myosin-binding protein C (cMyBP-C) remain poorly understood. In this...
In this study, we conducted a comprehensive analysis of the interactions between the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein and four neutralizing antibodies—S309, S304, CYFN1006, and VIR-7229. Using integrative computatio...
Evolutionary and functional studies suggested that the emergence of the Omicron variants can be determined by multiple fitness trade-offs including the immune escape, binding affinity for ACE2, conformational plasticity, protein stability and alloste...
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...
Next-generation sequencing (NGS) has revealed large numbers of genetic variants in LGMD-related genes, with most of them classified as variants of uncertain significance (VUSs). VUSs are genetic changes with unknown pathological impact and present a...
Nanobodies provide important advantages over traditional antibodies, including their smaller size and robust biochemical properties such as high thermal stability, high solubility, and the ability to be bioengineered into novel multivalent, multi-spe...
KRAS is a pivotal oncoprotein that regulates cell proliferation and survival through interactions with downstream effectors such as RAF1. Despite significant advances in understanding KRAS biology, the structural and dynamic mechanisms of KRAS allost...
The major histocompatibility complex (MHC) can recognize and bind to external peptides to generate effective immune responses by presenting the peptides to T cells. Therefore, understanding the binding modes of peptide–MHC complexes (pMHC) and...
MET exon 14 (METex14) skipping mutations differ from other non-small cell lung cancer (NSCLC) genomic biomarkers as they result in aberrantly spliced MET transcripts and increased MET-signaling. However, the most accurate method for their detection r...
While there is a consensus that the cytochrome b6f complex (cytb6f) in algae and plants is involved in the regulatory mechanism of oxygenic photosynthesis known as light-induced state transitions (STs), no such consensus exists for cyanobacteria. Her...
The GJB2 gene is the most common gene responsible for hearing loss (HL) worldwide, and missense variants are the most abundant type. GJB2 pathogenic missense variants cause nonsyndromic HL (autosomal recessive and dominant) and syndromic HL combined...
A growing body of experimental and computational studies suggests that the cross-neutralization antibody activity against Omicron variants may be driven by the balance and tradeoff between multiple energetic factors and interaction contributions of t...
The effective synthesis of N-benzyl cyclo-tertiary amines using imine reductase, key components in natural products and pharmaceutical synthesis, is a green approach. Traditional methods faced challenges with enzyme activity and selectivity. This stu...
Understanding the atomistic basis of multi-layer mechanisms employed by broadly reactive neutralizing antibodies of the SARS-CoV-2 spike protein without directly blocking receptor engagement remains an important challenge in coronavirus immunology. C...
RNA viruses are characterized by their extreme mutation rates, which play key roles in their biology and give them the ability to rapidly adapt to new environments. However, non-synonymous mutations tend to be largely deleterious to protein function,...
Influenza genes evolve mostly via point mutations, and so knowing the effect of every amino-acid mutation provides information about evolutionary paths available to the virus. We and others have combined high-throughput mutagenesis with deep sequenci...
Antivirals are used not only in the current treatment of influenza but are also stockpiled as a first line of defense against novel influenza strains for which vaccines have yet to be developed. Identifying drug resistance mutations can guide the cli...
The validation of a previously developed model of the interaction between the red pigment-concentrating hormone of Daphnia pulex and its cognate receptor (Jackson et al., IJBM 106, 969–978, 2018) was undertaken. Single amino acid replacements, notice...
Resistance to soybean cyst nematodes (SCN) in “Peking-type” resistance is bigenic, requiring Rhg4-a and rhg1-a. Rhg4-a encodes a serine hydroxymethyltransferase (GmSHMT08) and rhg1-a encodes a soluble NSF attachment protein (GmSNAP18). Re...
We present Annealed Mutational approximated Landscape (AMaLa), a new method to infer fitness landscapes from Directed Evolution experiments sequencing data. Such experiments typically start from a single wild-type sequence, which undergoes Darwinian...
Hypertrophic cardiomyopathy (HCM), caused by mutations in thin filament proteins, manifests as moderate cardiac hypertrophy and is associated with sudden cardiac death (SCD). We identified a new de novo variant, c.656A>T (p.D219V), in the TPM1 gen...
U2AF65 (U2AF2) and PUF60 (PUF60) are splicing factors important for recruitment of the U2 small nuclear ribonucleoprotein to lariat branch points and selection of 3′ splice sites (3′ss). Both proteins preferentially bind uridine-rich sequ...
Nicotinic acetylcholine receptors (nAChRs) are found throughout the mammalian body and have been studied extensively because of their implication in a myriad of diseases. α-Conotoxins (α-CTxs) are peptide neurotoxins found in the venom of...
The recent advances in artificial intelligence (AI) and machine learning have driven the design of new expert systems and automated workflows that are able to model complex chemical and biological phenomena. In recent years, machine learning approach...
The advent of targeted therapies has led to tremendous improvements in treatment options and their outcomes in the field of oncology. Yet, many cancers outsmart precision drugs by developing on-target or off-target resistance mechanisms. Gaining the...
We characterized a novel genetic variant c.292G > A (p.E98K) in the TPM1 gene encoding cardiac tropomyosin 1.1 isoform (Tpm1.1), found in a proband with a phenotype of complex cardiomyopathy with conduction dysfunction and slow progressive neuromu...
Hyperinsulinism is the most common cause of hypoglycemia in infants. In many cases conservative treatment is not effective and surgical intervention is required. Differentiation between diffuse and focal forms and localization of focal lesions are th...
Ataxia with oculomotor apraxia type 2 (AOA2), also known as autosomal recessive spinocerebellar ataxia with axonal neuropathy-2 (SCAN2) (OMIM #606002), is a neurodegenerative disorder characterized by early-onset progressive cerebellar ataxia, polyne...
Structural and biochemical studies have recently revealed a range of rationally engineered nanobodies with efficient neutralizing capacity against the SARS-CoV-2 virus and resilience against mutational escape. In this study, we performed a comprehens...
PARK2 mutations are the most common cause of early-onset Parkinson’s disease. No genotype-phenotype correlation exists, and phenotypic variability is quite common. We report two siblings with confirmed identical compound heterozygous mutations in the...
We report a probable pathogenic Thr119Ile mutation in presenilin-1 (PSEN1) in two unrelated Korean patients, diagnosed with early onset Alzheimer’s disease (EOAD). The first patient presented with memory decline when she was 64 years old. Magne...
COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has many variants that accelerated the spread of the virus. In this study, we investigated the quantitative effect of some major mutants of the spike protein of...
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