Ref E1
Computational Service
Confidence Reported
Scoped After Feasibility Review
Service Overview
Docking gives a static pose; molecular dynamics tells you whether that pose survives. We run all-atom simulations in explicit solvent — protein–ligand, protein–protein, membrane-embedded and nucleic acid systems — on timescales from a hundred nanoseconds to several microseconds, with replicate trajectories so that conclusions do not rest on a single run. Analysis is directed at the project question: whether a pose is stable, which contacts persist, how a mutation changes dynamics, or which conformational state dominates.
Key Features & Advantages
Replicates As Standard
Independent replicates with different seeds are run by default, because a single trajectory cannot distinguish a real effect from one sampling accident.
Careful System Preparation
Protonation states, metals, cofactors, membrane composition and ion concentration are set deliberately and documented, since most simulation failures originate in setup rather than sampling.
Analysis Aimed At Your Question
Rather than a standard panel of plots, the analysis is chosen to answer the specific question — pose stability, allosteric coupling, loop gating or interface persistence.
Convergence Reported Honestly
Every study states whether sampling converged. Where it did not, that is said plainly rather than concealed behind a smooth-looking average.
Where This Service Is Used
1Testing whether a docked pose is stable or drifts out of the pocket
2Understanding how a resistance mutation alters binding or protein dynamics
3Characterising loop or lid motions that gate access to an active site
4Studying a membrane protein in a realistic bilayer environment
5Generating conformational ensembles for ensemble docking or cryptic pocket discovery
Methods and Techniques Applied
1System building: protonation assignment, solvation, ion placement, membrane construction where required
2Force field selection and ligand parameterisation with validation of the generated parameters
3Staged minimisation, heating and equilibration with restraint release, followed by production simulation
4Replicate production runs in the hundred nanosecond to multi-microsecond range as scoped
5Trajectory analysis: RMSD, RMSF, hydrogen bonds, contact maps, secondary structure, distance and angle metrics
6Advanced analysis on request: principal component analysis, Markov state modelling, free energy landscapes, enhanced sampling
What We Need From You
1Structure of the system, experimental or modelled, with the ligand pose if one is to be simulated
2The specific question the simulation must answer, which determines length, replicates and analysis
3Environmental conditions: pH, ionic strength, membrane composition, temperature
4Any experimental observations the simulation should be tested against
What You Receive
1Trajectory files and the full set of input and parameter files needed to reproduce the run
2Analysis report with time-series plots, contact maps and structural interpretation
3Representative structures from clustering, with occupancy of each conformational state
4Movies and figures suitable for presentations and publications
5Convergence assessment and an explicit statement of what the sampling does and does not support
What We Compute and Report
1Structural deviation and per-residue fluctuation time series across every replicate
2Hydrogen bond occupancy and contact persistence for the interactions that matter to your question
3Conformational clusters with the population of each state and representative structures
4Secondary structure, distance, angle and lipid-interaction metrics selected for the system
5Convergence diagnostics and replicate agreement, reported whether or not they are favourable
Questions We Are Asked Before Scoping
How long should we simulate?
▸Long enough for the process of interest. Side-chain rearrangement needs nanoseconds, loop motion tens to hundreds of nanoseconds, domain motion microseconds or enhanced sampling. We scope the length to the question rather than to a default.
Does a stable trajectory prove the pose is correct?
▸No. It shows the pose is consistent with the force field over the simulated time. An incorrect pose can be metastable, which is why stability is used as a filter rather than as proof.
Can MD give binding affinity?
▸Not directly. Binding free energy requires end-point methods such as MM/GBSA or alchemical approaches such as FEP, both of which we offer as separate services.
Interpretation and Limitations
Computational predictions prioritise hypotheses; they do not independently establish binding, biological activity, therapeutic efficacy, safety or clinical validity. Performance depends on input quality, target class, the structural evidence available and the applicability domain of the selected methods. Scores used for ranking are comparative devices and should not be read as measured quantities. All deliverables are for research use only and are not intended for diagnostic or therapeutic use.
Is This the Right Service for You?
Choose this when
A docked or predicted pose is about to carry design decisions and has never been tested
The question concerns motion — loop gating, domain opening, membrane behaviour, allosteric coupling
A conformational ensemble is needed for ensemble docking or cryptic pocket work
Consider another service when
You need compounds ranked by binding strength rather than pose stability
MM/GBSA & MM/PBSA Binding Free Energy The question is which of several analogues to synthesise
Free Energy Perturbation 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.
Conclusions drawn from a single trajectory
Independent replicates with different seeds are standard, because one run cannot separate a real effect from a sampling accident.
A wrong protonation state quietly determining the result
Ionisation, histidine tautomers, metals and cofactors are assigned deliberately at setup and documented with the trajectory.
A stable trajectory presented as proof the pose is correct
Stability is reported as consistency with the force field over the simulated time — an incorrect pose can be metastable, and we say so.
A Worked Example
Testing two competing binding modes
The situation
Docking had produced two poses with indistinguishable scores, implying opposite design strategies.
What the work involved
Both complexes were built, equilibrated and simulated in triplicate, with contact persistence, ligand drift and hydrogen-bond occupancy tracked across replicates.
What came back
One pose lost its key contact within the first 40 ns in all three replicates; the other held for the full run. The surviving pose was carried into the design cycle, and the discriminating mutation was proposed.
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 Workflow
1
Scientific Consultation
We discuss the objective, the decision it supports and the data you hold. Nothing is quoted before we understand what the result has to answer.
2
Feasibility Review
We check that the data, target class and available structural evidence can support the proposed approach, and say plainly where they cannot.
3
Technical Proposal
Scope, methods, deliverables, timeline and price are confirmed in writing, together with the limitations we expect to report.
4
Computation and QC
The analysis runs on pinned tool versions in a containerised environment, with quality checkpoints and method comparison where that is informative.
5
Report and Follow-Up
You receive the ranked results, the documented methods, the limitations and a proposed validation plan, plus support in interpreting them.
Service Process
1
Online Consultation
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2
Solution Matching
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Service Contract
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Project Execution
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Data Delivery
Specifications & Turnaround
Note: ICDMO delivers computational (in silico) services. Results prioritise hypotheses for testing; they do not by themselves establish binding, biological activity, efficacy or safety. All deliverables are for research use only and are not intended for diagnostic or therapeutic use. Downstream experimental work is scoped separately and executed through qualified partners.
Get a Custom Quote
Our scientific team responds within 24 hours with a detailed technical proposal and pricing tailored to your project.
Contact Us Online ConsultationStandard Deliverables
✓Sequence-verified final product
✓Full QC documentation
✓Certificate of Analysis (CoA)
✓Electronic data files
✓Project completion report
Why ICDMO?
Computational CDMO Focus
Reproducible, Versioned Pipelines
Confidence & Limitations Reported
Experiment-Aware Recommendations
Response Within One Business Day