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We apply the methods of optimal experimental design to a differential equation model for epidermal growth factor receptor (EGFR) signaling, trafficking, and down-regulation. The model incorporates the role of a recently discovered protein…
The emergence of acquired drug resistance in cancer represents a major barrier to treatment success. While research has traditionally focused on genetic sources of resistance, recent findings suggest that cancer cells can acquire transient…
Fragment-based drug design is a promising strategy leveraging the binding of small chemical moieties that can efficiently guide drug discovery. The initial step of fragment identification remains challenging, as fragments often bind weakly…
Protein language models (pLMs) have demonstrated success at generating functional proteins across vast sequence spaces but lack the ability to design high-fitness variants on demand. Here, we iteratively guide pLMs toward user-defined…
The problem of reconstructing and identifying intracellular protein signaling and biochemical networks is of critical importance in biology today. We sought to develop a mathematical approach to this problem using, as a test case, one of…
With the rise of Transformers and Large Language Models (LLMs) in Chemistry and Biology, new avenues for the design and understanding of therapeutics have opened up to the scientific community. Protein sequences can be modeled as language…
With the advent of Information technology, the Bioinformatics research field is becoming increasingly attractive to researchers and academicians. The recent development of various Bioinformatics toolkits has facilitated the rapid processing…
Evolutionary therapy (ET) aims to steer tumor evolution by adjusting treatment timing and dosing to control rather than eradicate tumor burden. Clinical use requires reliable monitoring of tumor dynamics to inform mathematical models that…
Experimental evidence indicates that human brain cancer cells proliferate or migrate, yet do not display both phenotypes at the same time. Here, we present a novel computational model simulating this cellular decision-process leading up to…
G protein-coupled receptors (GPCRs) govern diverse physiological processes and are central to modern pharmacology. Yet discovering GPCR modulators remains challenging because receptor activation often arises from complex allosteric effects…
There is a widening recognition that cancer cells are products of complex developmental processes. Carcinogenesis and metastasis formation are increasingly described as systems-level, network phenomena. Here we propose that malignant…
Practically, all chemotherapeutic agents lead to drug resistance. Clinically, it is a challenge to determine whether resistance arises prior to, or as a result of, cancer therapy. Further, a number of different intracellular and…
Aim: In the present work, we aimed to evaluate a comprehensive radiomics framework that enabled prediction of EGFR and KRAS mutation status in NSCLC cancer patients based on PET and CT multi-modalities radiomic features and machine learning…
Epidermal growth factor (EGF), a potent cytokine, is known to promote tumor invasion both in vivo and in vitro. Previously, we observed that single breast tumor cells (MDA-MB-231 cell line) embedded within a 3D collagen matrix displayed…
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…
Conventional drugs work, as a rule, by inhibiting the enzymatic activity of specific proteins, capping their active site. In this paper we present a model of non- conventional drug design based on the inhibiting effects small peptides…
Evolutionary algorithms have long been used for optimization problems where the appropriate size of solutions is unclear a priori. The applicability of this methodology is here investigated on the problem of designing a nano-particle (NP)…
Multidrug resistance consists of a series of genetic and epigenetic alternations that involve multifactorial and complex processes, which are a challenge to successful cancer treatments. Accompanied by advances in biotechnology and…
The regulation of a gene depends on the binding of transcription factors to specific sites located in the regulatory region of the gene. The generation of these binding sites and of cooperativity between them are essential building blocks…
Learning how proteins fold will hardly have any impact in the way conventional -- active site centered -- drugs are designed. On the other hand, this knowledge is proving instrumental in defining a new paradigm for the identification of…