SUMMARY The Multi-scale Computational Modeling (MCM) Core will continue to provide essential expertise and infrastructure in the area of multi-scale and multi-discipline computational modeling of bioengineering and biomedical problems, with a new addition of Artificial Intelligence/Machine Learning (AI/ML) capacities for big data driven modeling in the COBRE Phase II. Key to Virtual Human Trials, the organizing concept of SC-TRIMH, is to develop predictive multi-scale models of the human body for assessing new interventions, devices, and therapeutics. As its main mission, this core will support our SC-TRIMH investigators in all their computation and simulation needs at molecular, cellular, tissue, body, and population levels toward improving musculoskeletal health. Additionally, it will provide mentoring and strategic planning to all SC-TRIMH investigators and associates, especially those who do not have primary expertise in the areas of multi-scale computational modeling, AI/ML, or using cluster parallel computing to maximize their computational outcome. Thus, investigators will be advised on best approaches, model building strategies, and software settings to take full advantage of Clemson University's cluster parallel computing capabilities and extensive AI/ML research capacity. Furthermore, we will strive to build the MCM Core into the “go-to place” that facilitates comprehensive computational bioengineering research for investigators from across South Carolina, in the southeast, the nation, and around the world. Specifically, the MCM core will maintain and develop the most advanced software tools and packages to enable SC-TRIMH investigators to perform computational bioengineering and biomedical modeling at molecular, cellular, tissue, body, and population levels (Aim 1); the MCM core will tune and expand the current set of computational tools and packages to integrate AI/ML based modeling so that they will run on Clemson's Palmetto Cluster (Aim 2); the MCM core will enhance standard and project-specific assistance and mentoring to the COBRE Research Project Leaders (RPLs), other SC-TRIMH investigators, and their team, especially those who do not have primary expertise in modeling of complex problems (Aim 3); the MCM core will further promote the MCM Core as a leading resource and the “go-to place” for researchers from Clemson University, South Carolina, the southeast region and beyond for all multi-scale and multi-discipline computational modeling of complex bioengineering and biomedical problems at cellular, tissue, body, and population levels with special emphasis on expertise in building patient-specific or cohort-based musculoskeletal systems (Aim 4). Since the inception of the MCM core, the number of projects utilizing the Core has significantly increased each year. During Phase II, we will further develop the core capacities by acquisition and development of new software tools and packages for AI/ML-based modeling and its integration ...