No Reagents for the In Silico Phase
Confidence-Scored Results
Publication-Ready Figures
Validation Planned With Partners
Response Within One Business Day
Service Overview
ICDMO provides molecular dynamics (MD) simulation for protein complexes and protein–small molecule interactions. MD simulation uses 3D structures (PDB format) as initial models with classical force fields to describe atomic interactions, dynamically tracking atom trajectories to reveal binding and dissociation processes, interface rearrangement, conformational transitions, and key residue contributions to stability. Simulations run on GPU-accelerated HPC with pinned software versions, so results are reproducible and the parameters behind them are on record. Where experimental follow-up is warranted — Y2H, Co-IP, SPR, MST, BLI or ITC — we design the validation plan with you and coordinate it through partner laboratories.
Technical Advantages
✓
High-Performance Computing
GPU-accelerated HPC with pinned software versions delivers reproducible simulations. Accessible timescales depend on system size and are agreed during scoping rather than promised in advance.
✓
Publication-Grade Visualizations
RMSD, RMSF, H-bond networks, and energy heatmaps formatted for top-tier journal submission.
✓
Expert Team
Scientists with decades of combined MD experience covering proteins, nucleic acids, and small molecules.
✓
Validation Planned, Not Assumed
We translate simulation output into a focused validation plan — Y2H, Co-IP, SPR, MST, BLI or ITC — and coordinate the work through partner laboratories.
✓
Customizable Parameters
Temperature gradients (50–80°C), metal ions, membrane systems, and special force field setups.
✓
Comprehensive Energy Analysis
MM/GBSA binding free energy with per-residue and per-ligand moiety decomposition.
Technical Principle
A validated biomolecular force field is applied to the protein, with small molecules parameterised and charges derived by an established semi-empirical scheme. Systems are solvated in an explicit water box with a 10 Å buffer, neutralised with counter-ions, then taken through energy minimisation, controlled heating to 300 K, constant-pressure density equilibration and unrestrained production simulation of 50–400 ns with coordinates written every 10 ps. Every parameter is recorded and delivered with the trajectory.
Applications
Protein–Protein MD Simulation
▸Dynamic interaction mechanism capture across entire simulation timescale
▸Mutation & stability assessment — predict effect of point mutations on binding affinity
▸Experimental guidance: identify key residues for targeted mutagenesis or inhibitor design
▸Publication-quality structural visualizations of binding interface dynamics
Protein–Small Molecule MD Simulation
▸Binding mechanism analysis: pose stability, induced-fit effects, key pharmacophore contacts
▸Structure–activity relationship (SAR) studies and lead optimization
▸Experimental validation support: suggest optimal labeling/mutation sites for biophysical assays
▸Publication-ready RMSD, RMSF, H-bond occupancy, and 2D interaction diagrams
Trajectory Analysis Methods
1RMSD (Root Mean Square Deviation) — quantifies structural deviation from the reference frame over simulation time
2RMSF (Root Mean Square Fluctuation) — identifies flexible vs. stable regions at residue/atom level
3Hydrogen Bond Analysis — donor–acceptor distance (<3.5 Å), angle (<35°), bond counts, lifetimes, and spatial distribution
4MM/GBSA Binding Free Energy — van der Waals, electrostatic, and solvation contribution breakdown
5Per-residue energy decomposition — identifies dominant stabilizing/destabilizing residues
6B-factor analysis and conformational change mapping
Sample Requirements
1Protein–Protein: PDB file of docked complex + sequence information (≤800 aa total recommended)
2Protein–Ligand: 3D ligand structure (mol2 / sdf / pdb) + 2D chemical structural diagram
3Sequence-only submissions: require upstream AOS / molecular docking service prior to MD
4High-resolution, complete structures strongly preferred; partial structures evaluated case-by-case
What We Need From You
1Structure of the system, experimental or modelled, including the ligand pose if one is to be simulated
2The specific question the simulation must answer, which sets the length, replicate count and analysis
3Environmental conditions: pH, ionic strength, temperature and membrane composition where relevant
4Ligand structures and any existing parameters, along with protonation states if they are known
5Experimental observations the simulation should be tested against, such as HDX, NMR or mutational data
How the Analysis Is Performed
1System building: protonation assignment, solvation, ion placement and membrane construction where required
2Force field selection and ligand parameterisation, with validation of the generated parameters
3Staged minimisation, heating and equilibration with gradual restraint release before production
4Replicate production simulation with independent seeds across the agreed aggregate timescale
5Trajectory analysis: RMSD, RMSF, hydrogen bonding, contact maps, secondary structure and custom metrics
6Advanced analysis where scoped: principal component analysis, Markov state models, free energy landscapes and enhanced sampling
What You Receive
1Trajectory files together with the complete input, topology and parameter set needed to reproduce the run
2Analysis report with time-series plots, contact maps and structural interpretation of the findings
3Representative structures from clustering, with the occupancy of each conformational state
4Movies and publication-quality figures of the behaviour observed
5Convergence assessment and an explicit statement of what the sampling does and does not support
Interpretation and Limitations
A stable trajectory shows that a structure is consistent with the force field over the simulated time; it does not prove a binding mode is correct, since incorrect poses can be metastable. Force fields approximate real physics, timescales remain short relative to many biological processes, and single trajectories cannot distinguish a real effect from a sampling accident — which is why replicates and convergence assessment are standard. Binding affinity requires MM/GBSA or alchemical free energy methods rather than plain dynamics.
Questions We Are Asked Before Scoping
How long should the simulation be?
▸Long enough for the process of interest: side-chain rearrangement needs nanoseconds, loop motion tens to hundreds, domain motion microseconds or enhanced sampling. We scope the length to the question rather than to a default.
Will you tell us if the result is inconclusive?
▸Yes. Where sampling has not converged or where replicates disagree, that is stated plainly rather than hidden behind a smooth-looking average.
Can we continue the simulations ourselves afterwards?
▸Yes. Complete input, topology and parameter files are delivered so your team can extend, repeat or repurpose the system without rebuilding it.
Technical Workflow
1
Data Preparation & System Setup
Receive the structure, assign protonation states and force field parameters for protein and ligand, add hydrogens, solvate in an explicit water box with a 10 Å buffer and neutralise with counter-ions.
2
Energy Minimization
Remove steric clashes and relax geometry using positional restraints on backbone. Optimize water/ions first. Up to 5,000 steps.
3
Heating (0 K → 300 K)
Gradually increase temperature using Langevin thermostat. Backbone restraints maintained. ~50,000 steps (2 fs timestep). Optional temperature gradient (50–80°C).
4
NPT Equilibration
Equilibrate under constant pressure (1 atm) and temperature (300 K). Gradually release backbone restraints over 100–200 ps.
5
Production MD Run
Unrestrained production MD for 50–400 ns. Trajectory snapshots output every 10 ps.
6
Trajectory Analysis & Reporting
cpptraj + VMD analysis: RMSD, RMSF, H-bonds, MM/GBSA free energy. Deliver publication-grade figures and comprehensive report.
Service Timeline & Deliverables
Is This the Right Service for You?
Choose this when
A structure or pose needs testing for stability before it carries decisions
Conformational behaviour, loop motion or membrane interaction is the question
An ensemble is needed for downstream docking or pocket discovery
Consider another service when
Compound ranking rather than dynamics is required
MM/GBSA & MM/PBSA Binding Free Energy A structure is needed in the first place
AI Protein Structure Prediction What Goes Wrong, and How We Handle It
These are the failure modes that produce confident-looking results which do not survive the next experiment. Each one is designed against rather than discovered afterwards.
One trajectory used to support a mechanistic claim
Replicates are standard and convergence is reported, including when it was not reached.
Setup decisions made silently by default
Protonation, ions, membrane composition and parameterisation are chosen deliberately and delivered with the trajectory.
Simulation length chosen by convention rather than by the process studied
Timescale is scoped to the motion in question, and enhanced sampling is proposed where plain dynamics cannot reach it.
A Worked Example
Testing a predicted complex before designing against it
The situation
A predicted protein–ligand complex was about to become the basis of a design programme.
What the work involved
The system was built with explicit protonation decisions, equilibrated in stages and simulated in triplicate, with contact persistence and ligand drift tracked across replicates.
What came back
Two of three replicates lost the principal hydrogen bond within 60 ns. The pose was reported as unreliable, and an alternative binding mode was proposed and tested before chemistry began.
Illustrative of the shape this work takes. Details are generalised, no client or target is identified, and scope and outcome vary with the system in question.
What Published Work Reports
The results below were published by independent groups and are cited to show what these computational approaches have achieved in the literature. They are not ICDMO project results, and outcomes vary substantially between targets, datasets and programmes. We do not promise comparable results for any particular project.
Alchemical free energy calculations reach roughly 1 kcal/mol error
Benchmark studies on congeneric series across multiple drug targets report root-mean-square errors around 1 kcal/mol, with published protocol work reporting prediction errors below approximately 1.3 kcal/mol on test sets of ligand transformations. An error of this size is small enough to separate compounds differing by roughly one order of magnitude in affinity, which is what makes the method useful for deciding which analogue to synthesise.
Protocol and benchmark studies, Scientific Reports, 2019 ↗Accuracy is system-dependent, and retrospective benchmarks flatter it
Reviews of free energy methods in drug discovery note that much of the published evidence is retrospective, and that prospective performance in live optimisation campaigns is less thoroughly documented. This is why we validate against your own measured compounds before issuing prospective predictions, rather than quoting a literature error bar as though it applied to your system.
Review, Free Energy Calculations for Drug Discovery, 2021 ↗Service Process
1
Online Consultation
2
Solution Matching
3
Service Contract
4
AI Computation
5
Project Report
Note: All services are for research use only and not intended for diagnostic or therapeutic purposes.
Get a Custom Quote
Our scientific team responds within 24 hours with a detailed technical proposal and pricing tailored to your research goals.
Contact Us Online ConsultationStandard Deliverables
✓Detailed analysis report (PDF)
✓Raw data files & processed outputs
✓High-resolution publication figures
✓Interaction scoring tables (Excel)
✓Project summary presentation
Related AI Services
AI-Powered Digital Library-to-Library ScreeningProtein Interaction & Binding Site PredictionAI Multimodal Protein–Compound ScreeningDigital Protein/Nucleic Acid Interaction ModelVHH Antibody AI Screening & ValidationAI Digital Library ConstructionWhy ICDMO AI?
Computational CDMO Focus
Reproducible, Versioned Pipelines
Confidence & Limitations Reported
Response Within One Business Day