Molsoft ICM-Pro V3.9-5 (x64) – Molecular Modeling Software

MolSoft ICM-Pro v3.9-5 (x64)

MolSoft ICM-Pro v3.9-5 is a professional molecular modeling and computational drug discovery platform designed for researchers working in structural biology, computational chemistry, medicinal chemistry, and computer-aided drug design. The software provides an integrated environment for analyzing protein structures, modeling molecular interactions, docking ligands, exploring chemical space, and optimizing potential drug candidates.

Version 3.9-5 represents a major release for the ICM-Pro platform, introducing new artificial intelligence and physics-based capabilities for structure-based drug discovery, lead optimization, and ultra-large chemical space exploration. MolSoft describes the release as a significant update that expands the platform’s ability to combine AI-driven molecular design with established computational modeling methods.

What Is ICM-Pro?

ICM-Pro is MolSoft’s advanced desktop environment for molecular modeling and structure-based drug design. It is built around MolSoft’s Internal Coordinate Mechanics methodology and brings a range of computational chemistry and structural biology tools together in a single application.

The platform can be used to inspect protein structures, study binding pockets, analyze molecular interactions, model ligands, perform docking calculations, investigate protein-protein interactions, and support virtual screening projects. Its capabilities make it suitable for both academic research and professional pharmaceutical and biotechnology workflows.

What’s New in Version 3.9-5?

The 3.9-5 release introduces several major technologies designed to improve the speed and intelligence of molecular design workflows. These additions focus particularly on large-scale screening, fragment and ligand optimization, generative AI, peptide modeling, and chemical database searching.

CombiRIDGE – High-Throughput Combinatorial Docking

CombiRIDGE is a GPU-accelerated workflow designed for high-throughput screening of combinatorial chemical libraries. The system starts from a pre-docked three-dimensional anchor and associated two-dimensional R-groups, then generates complete three-dimensional conformations directly within the protein binding site.

The generated poses can be refined using GPU acceleration and evaluated using RTCNN scoring. This workflow is designed to support rapid R-group optimization while preserving important ligand-protein interactions.

groupGen – AI-Assisted Lead Optimization

groupGen introduces a generative neural-network approach for proposing R-group substitutions in the context of a protein binding site. It uses a three-dimensional representation of the local receptor environment to generate chemically realistic substituents that can fit the surrounding binding pocket.

This type of workflow can help researchers explore structure-activity relationships more efficiently by generating candidate modifications that are evaluated in the context of the target binding environment.

Ligand AIDE – De Novo Ligand Design

Ligand AIDE provides an AI-driven evolutionary workflow for de novo ligand generation. Starting with docked fragments, the system can iteratively grow and optimize compounds through multiple generations.

The workflow combines generative substitutions, re-docking, and selection based on binding quality, drug-like characteristics, and synthesizability. This creates an integrated approach for exploring new molecular structures while keeping the target binding site as part of the design process.

Advanced 3D Ligand Editing

ICM-Pro includes an interactive three-dimensional ligand modeling environment that allows researchers to manipulate molecular structures directly within a binding site. Version 3.9-5 expands this environment with more comprehensive peptide modeling capabilities.

The updated functionality includes residue-level editing, continuous-chain handling, peptide-receptor co-minimization, RTCNN scoring, secondary-structure refinement, and support for stapled peptide modeling.

These capabilities are particularly relevant to researchers working with peptide therapeutics and protein-peptide interactions, where molecular flexibility and three-dimensional geometry can play an important role in computational modeling.

GigaSearch v2.0

GigaSearch v2.0 expands ICM-Pro’s ability to search extremely large chemical spaces. MolSoft describes the technology as an efficient approach for similarity and substructure searching across massive chemical libraries.

The current GigaSearch ecosystem provides access to very large databases, including the Enamine Space and Chemspace Freedom Space. MolSoft states that ultra-large substructure searches can be performed rapidly using optimized fingerprints and statistical pruning techniques.

For researchers involved in virtual screening and analog discovery, the ability to search massive chemical spaces can be an important part of finding chemically related structures and expanding potential hit series.

Protein Structure Analysis

ICM-Pro provides tools for examining and analyzing protein structures. Researchers can work with structural data, inspect molecular geometry, investigate binding pockets, create molecular surfaces, analyze electrostatic properties, and study interactions between proteins and ligands.

The platform also provides access to structural and sequence information and supports workflows where protein structures need to be prepared and analyzed before docking or virtual screening.

Molecular Docking

Molecular docking is one of the core capabilities associated with ICM-Pro. The platform supports ligand docking and a range of structure-based modeling workflows for investigating how candidate molecules may interact with a target protein.

MolSoft’s docking technology incorporates its optimized force field and Biased Probability Monte Carlo methodology. The software can also represent receptor flexibility through its four-dimensional docking approach, allowing ensembles of receptor structures to be considered in appropriate workflows.

These capabilities are designed to help researchers evaluate possible ligand binding modes and prioritize compounds for further investigation.

Virtual Ligand Screening

ICM-Pro can be used as part of virtual ligand screening workflows in which large compound libraries are computationally evaluated against a molecular target.

A hierarchical screening strategy can be used to accelerate the evaluation of very large libraries. Candidate compounds can first be processed using computationally efficient methods before promising hits are subjected to more detailed docking and scoring.

This type of workflow is particularly useful in early-stage computational drug discovery, where researchers may need to examine large numbers of candidate molecules before selecting a smaller group for experimental validation.

AI and Physics-Based Drug Discovery

One of the most notable aspects of ICM-Pro v3.9-5 is the combination of AI-driven workflows with physics-based molecular modeling.

Generative neural networks can help propose new molecular structures or substituents, while docking, scoring, molecular mechanics, and other computational methods provide additional criteria for evaluating those structures.

This combination allows researchers to explore chemical space from multiple perspectives rather than relying exclusively on either generative AI or traditional molecular modeling.

Lead Optimization

Lead optimization is a major application area for ICM-Pro. Once an initial molecular hit has been identified, researchers often need to explore structural modifications that may improve potency, selectivity, physicochemical properties, or synthetic feasibility.

Version 3.9-5 introduces several workflows that can assist with this process by exploring R-group substitutions, generating new analogs, docking candidate structures, and ranking molecules according to multiple computational criteria.

The result is a more integrated workflow for moving from an initial molecular concept toward a more refined candidate series.

Cheminformatics and Chemical Searching

Large-scale chemical searching is another important part of the ICM ecosystem. Researchers can work with molecular databases and perform similarity or substructure searches to identify related compounds and potential analogs.

GigaSearch extends this capability to chemical spaces containing billions or even hundreds of billions of compounds. This provides a practical way to investigate enormous virtual libraries without requiring every compound to be fully enumerated and stored locally.

Applications in Drug Discovery

ICM-Pro can support multiple stages of computational drug discovery, including:

• Protein structure preparation and analysis.
• Binding-site and pocket investigation.
• Small-molecule docking.
• Protein-protein docking.
• Protein-peptide modeling and docking.
• Virtual ligand screening.
• Structure-based lead optimization.
• De novo ligand design.
• Large-scale chemical similarity searching.
• Substructure searching.
• Ligand-protein interaction analysis.
• Computational exploration of chemical libraries.

Research and Scientific Workflows

ICM-Pro is designed to fit into research workflows where computational predictions need to be connected with experimental chemistry and biology. Researchers can use structural models and docking results to generate hypotheses, prioritize compounds, investigate binding interactions, and guide subsequent experimental work.

The platform has been used in published scientific research and modern structure-based drug discovery projects. MolSoft reports recent applications of ICM-Pro in large-scale virtual screening, molecular modeling, ligand optimization, and the exploration of extremely large chemical spaces.

Why ICM-Pro v3.9-5 Is Important

The development of computational drug discovery increasingly involves very large molecular databases, complex protein targets, AI-generated chemical structures, and sophisticated molecular simulations. ICM-Pro v3.9-5 addresses several of these challenges by bringing AI-assisted molecular generation, GPU-accelerated docking, peptide modeling, and giga-scale chemical searching into a unified environment.

For researchers, the main advantage is the ability to move between different stages of computational analysis without relying on completely separate software packages for every task.

Typical Users

ICM-Pro is intended for professional and academic users working in areas such as:

• Computational chemistry.
• Structural biology.
• Medicinal chemistry.
• Computer-aided drug design.
• Pharmaceutical research.
• Biotechnology research.
• Molecular modeling.
• Virtual screening.
• Protein-ligand interaction studies.
• Academic research and drug discovery programs.

ICM-Pro v3.9-5 at a Glance

Feature	Description
Product	MolSoft ICM-Pro
Version	3.9-5
Architecture	x64
Primary Focus	Computational chemistry and structure-based drug discovery
AI Workflows	groupGen, Ligand AIDE and neural-network-based scoring workflows
Docking	Ligand, protein-protein and peptide-related docking workflows
Chemical Search	GigaSearch v2.0 for ultra-large chemical spaces
Modeling	Protein, ligand and peptide modeling
Acceleration	GPU-accelerated workflows including CombiRIDGE

Conclusion

MolSoft ICM-Pro v3.9-5 (x64) is a comprehensive platform for computational molecular research and modern structure-based drug discovery. Its combination of molecular modeling, docking, virtual screening, AI-assisted ligand design, peptide modeling, and large-scale chemical searching makes it a powerful environment for researchers working with complex biological targets and chemical libraries.

The 3.9-5 release is particularly notable for expanding the role of artificial intelligence within the ICM workflow while maintaining MolSoft’s physics-based modeling and scoring technologies. Features such as CombiRIDGE, groupGen, Ligand AIDE, expanded peptide modeling, and GigaSearch 2.0 make this version an important update for computational chemistry and drug discovery workflows.

For researchers who work with protein structures, molecular docking, ligand optimization, virtual screening, or large chemical databases, ICM-Pro provides an integrated environment capable of supporting a wide range of computational experiments and discovery workflows.

Official developer: MolSoft LLC