ICM-Pro

ICM-Pro Desktop Modeling, developed by Molsoft L.L.C., is a state-of-the-art physics-based and AI-powered desktop software environment designed for biologists and chemists working in structural biology, drug discovery, and computational chemistry. Available on Windows, Linux, and Mac OSX, ICM-Pro provides direct access to sequence and structural databases, enabling users to analyze sequences and alignments, inspect protein structures, study pockets and bound ligands, create molecular surfaces, calculate electrostatics, make mutations, and perform advanced docking and ligand design workflows.

ICM-Pro is extensible through optional add-ons including ICM-Homology, ICM-Chemist-Pro, and ICM-VLS, making it a flexible platform suitable for a wide range of computational life sciences applications. Its methods are grounded in peer-reviewed science, with foundational algorithms published in leading journals since 1994.

Small Molecule Docking and Ligand Design

• Performs fast and accurate docking of fully continuously flexible small molecule ligands to proteins represented by grid interaction potentials.
• Includes built-in procedures to account for induced fit, such as multiple receptor docking (4D docking) and explicit receptor docking.
• Features the ICM 3D Ligand Editor, developed in collaboration with medicinal chemists at Novartis, which allows interactive editing of a chemical structure inside a receptor binding pocket in both 2D and 3D.
• Modifications to ligand atoms and groups are evaluated on the fly, with binding energy and score updated in real time upon each change.
• Changes are stored with full undo and redo functionality; approved modifications can be tagged and saved to a chemical spreadsheet.
• Ligand binding score predictions are powered by MolSoft's high-accuracy ICM docking engine.

Pocket and Binding Site Identification

• ICM Pocket Finder identifies ligand binding sites in any protein, DNA, or RNA structure using grid potential maps of van der Waals interactions.
• Surfaces are contoured and physical properties of identified pockets are calculated and tabulated.
• A drug-likeness score is provided for each identified pocket.

Molecular Dynamics

• ICM-Pro includes built-in support for OpenMM, a GPU-accelerated molecular dynamics engine.
• Achieves fast MD simulations of 3–12 ps/s (or 0.2–1.0 μs/day) on a cost-effective workstation GPU.
• Provides a direct binary interface to OpenMM for seamless transfer of ICM molecular objects to the MD engine.
• Automatically collects MD trajectory snapshots into the ICM conformational stack for further analysis and visualization.

Protein Structure Analysis and Crystallographic Tools

• Direct link to the Protein Data Bank (PDB) for downloading and analyzing protein structures.
• Supports building Ramachandran plots, superimposing multiple structures, analyzing distances and angles, calculating contact and surface areas, and displaying hydrogen bonds.
• Builds electrostatic surfaces and calculates ligand binding pockets.
• Crystallographic analysis tools allow evaluation of the full biological unit, assessment of crystal-crystal contacts, and contouring of electron density maps to assess ligand occupancy in the active site.

Protein-Protein Docking and Interaction Site Prediction

• Contains a well-validated protein-protein docking algorithm that has consistently performed well in the worldwide CAPRI protein-protein docking competition.
• Includes an algorithm to predict protein-protein docking interaction sites using the Optimal Docking Area method.

PROTAC Modeling

• Automatically and accurately models the tripartite complex of a target protein, PROTAC molecule, and E3 ligase.

Protein Structure Prediction and Mutation Analysis

• Includes procedures to regularize or build protein backbones, optimize side-chains and loops by global energy optimization, and simulate small peptide folding.
• Predicts the effect of mutations on protein stability and on protein-protein, protein-peptide, and protein-ligand binding interactions.

Bioinformatics and Sequence Analysis

• Includes all tools from ICM-Bio for searching sequence databases using high-quality global pairwise and multiple alignment algorithms.
• Supports pattern, Prosite, and profile searches.
• Produces evolutionary trees, principal component views, annotation transfer from sequence to structures, threading, and alignment visualization.

Electrostatics

• ICM-REBEL solves the Poisson equation for molecules of any size using a boundary element algorithm that does not depend on any grid and uses the exact analytical molecular surface as the boundary.
• Calculates accurate electrostatic potential and generates a 3D surface skin model colored by potential with exact positions of electric charges.

Chemistry Tools and Molecular Graphics

• Chemicals can be sketched in the ICM Molecular Editor and viewed in a chemical spreadsheet.
• Includes all molecular graphics tools from ICM-Browser-Pro, accessible via a GUI interface.
• Supports display modes including wire, CPK, ball-and-stick, worm, ribbon, accessible surface, transparent molecular surface, perspective, depth cueing, and smooth and rugged solid surfaces.
• Supports hardware stereo, side-by-side stereo, and Anaglyph stereo visualization.

ICM-Pro is a comprehensive desktop platform combining physics-based modeling, AI-driven predictions, and GPU-accelerated simulation in a single integrated environment. Its broad feature set, cross-platform availability, and extensibility through add-ons make it well suited for research teams in structural biology, medicinal chemistry, and computational drug discovery.