Jan 2026· Journal of Chemical Information and Modeling· 0 citations· 67 references
Computer ScienceMedicine
Abstract
Molecular glues, including protein degraders and protein-protein interaction (PPI) stabilizers, have emerged as a new paradigm of drug design for regulating interactions between biomacromolecules; yet it is still a challenge for rational design of molecular glues. KRAS, as a prevalent oncogenic driver, is notoriously difficult to target by traditional small molecular drugs due to its challenging binding surface and frequent mutations. Although the small molecular drug RMC7977 has been designed as a PPI stabilizer for stabilizing the inherently weak RAS-CYPA interaction, the precise molecular mechanism underlying its stabilization effect and selectivity difference requires a deeper understanding. To this end, we leverage an integrated computational strategy combining molecular dynamics (MD) simulation, end-point binding free-energy calculation, and enhanced sampling technologies to elucidate the dynamic characteristics of RAS-ligand-CYPA interactions. Our result exhibits a high correlation between the predicted binding affinities and the experimental observations, demonstrating that RMC7977, acting as a strong PPI stabilizer, significantly enhances the stability of the KRAS-CYPA interaction, where, by delicately remodeling the protein-protein interface, the drug optimizes various interactions. Moreover, the results also uncover the dynamic process of stabilizer-mediated KRAS-CYPA stabilization and the mechanistic origin of the binding selectivity. This study provides essential molecular-level insights into RMC7977's function and offers a valuable computational framework for evaluating the stabilization effect of ligands targeting the KRAS-CYPA and other challenging PPI systems.
Agile - denoting "the quality of being agile, readiness for motion, nimbleness, activity, dexterity in motion" - software development methods are attempting to offer an answer to the eager business community asking for lighter weight along with faster and nimbler software development processes. This is especially the case with the rapidly growing and volatile Internet software industry as well as for the emerging mobile application environment. The new agile methods have evoked substantial amount of literature and debates. However, academic research on the subject is still scarce, as most of existing publications are written by practitioners or consultants. The aim of this publication is to begin filling this gap by systematically reviewing the existing literature on agile software development methodologies. This publication has three purposes. First, it proposes a definition and a classification of agile software development approaches. Second, it analyses ten software development methods that can be characterized as being "agile" against the defined criterion. Third, it compares these methods and highlights their similarities and differences. Based on this analysis, future research needs are identified and discussed.
P. Abrahamsson, O. Salo, Jussi Ronkainen et al.· arXiv.org· 728 citations· ⚡54
Context: Software startups are newly created companies with no operating history and fast in producing cutting-edge technologies. These companies develop software under highly uncertain conditions, tackling fast-growing markets under severe lack of resources. Therefore, software startups present a unique combination of characteristics which pose several challenges to software development activities. Objective: This study aims to structure and analyze the literature on software development in startup companies, determining thereby the potential for technology transfer and identifying software development work practices reported by practitioners and researchers. Method: We conducted a systematic mapping study, developing a classification schema, ranking the selected primary studies according their rigor and relevance, and analyzing reported software development work practices in startups. Results: A total of 43 primary studies were identified and mapped, synthesizing the available evidence on software development in startups. Only 16 studies are entirely dedicated to software development in startups, of which 10 result in a weak contribution (advice and implications (6); lesson learned (3); tool (1)). Nineteen studies focus on managerial and organizational factors. Moreover, only 9 studies exhibit high scientific rigor and relevance. From the reviewed primary studies, 213 software engineering work practices were extracted, categorized and analyzed. Conclusion: This mapping study provides the first systematic exploration of the state-of-art on software startup research. The existing body of knowledge is limited to a few high quality studies. Furthermore, the results indicate that software engineering work practices are chosen opportunistically, adapted and configured to provide value under the constrains imposed by the startup context.
Nicolò Paternoster, Carmine Giardino, M. Unterkalmsteiner et al.· Information and Software Tec...· 394 citations· ⚡54
The new ChartNet training dataset could improve the accuracy of vision-language models that help analyze business trends or interpret scientific figures.
