SILCS
Site-Identification by Ligand Competitive Saturation (SILCS) generates 3-D maps (FragMaps) of interaction patterns for chemical functional groups with your target molecule.
INNOVATIVE LIGAND DESIGN & OPTIMIZATION WITH SILCS
Site-Identification by Ligand Competitive Saturation (SILCS) generates 3-D maps (FragMaps) of interaction patterns for chemical functional groups vvith your target molecule.
SILCS reveals intricacies of dynamics and provides tools to optimize ligand scaffolds using qualitative and quantitative binding pockets insights allowing more rapid and effective drug design.
SILCS: ENHANCED MIXED SOLVENT MD
SILCS uses multiple small molecule probes with various functional groups, explicit solvent modeling, and target molecule flexibility to perform protein target mapping.
A Grand Canonical Monte Carlo approach drives probe sampling beyond the limits of diffusion and makes SILCS particularly useful for probing cryptic/transient binding pockets.
LET FRAGMAPS GUIDE YOUR LEAD DISCOVERY
Conveniently explore FragMaps in our user interface or in your favorite molecular visualization software, including Autodock Tools, Pymol MOE, and VMD.
Visualize favorable interactions with the target macromolecule.
Gain insights to design better ligands with optimally placed functional groups.
FragMap of p38 MAP kinase-ligand complex colored by fragment type: green = apolar, red = H-bond acceptor, blue = H-bond donor & cyan = positive charge. FragMap densities near the bound inhibitor provide options of ligand optimization.
USER INTERFACE
New point-and-click approach to soluble protein system is preparation, job submission to remote host and progress tracking, and results visualization.
INSIGHTFUL
SILCS enables discovery of deep binding pockets in proteins & enzymes including membrane bound proteins.
In this GPCR SILCS correctly predicts functional group affinities of a known ligand while simultaneously offering optimization solutions for this ligand. This approach has identified novel agonists of the β2-Adrenergic Receptor.
VERSATILE
SILCS enables discovery of deep binding pockets in proteins & enzymes including membrane bound proteins.
EASY TO USE
A command-line tool automates setup for transmembrane proteins (GPCRs and more).
CGENFF
The CHARMM General Force Field program generates comprehensive parameters and topology information for a wide range of drug-like molecules, allowing their use in computer-aided drug design campaigns.
RAPID AUTOMATION
Comprehensive Topology Generation and Parameter Assignment for Organic Molecules
The CHARMM General Force Field (CGenFF) program enables use of a wide range of diverse drug-like molecules in computer-aided drug design efforts.
Obtain parameter and topology files for organic molecules in less than 0.01s with this rapid, automated tool!
These comprehensive parameter files contain the information on atom connectivities, atom charges, atom types, bond angles, dihedral angles, bond force constants, and the empirical force field parameters required for a range of molecular modeling methods, molecular dynamics simulation packages and related technologies.
EASY TO USE
Input molecular structure in MOL2 format, CGenFF does the rest!
WIDE COVERAGE
CGenFF can be used for >90% of drug-like molecules.
COMPATIBLE
Parameter output format is compatible with CHARMM force fields & a range of modeling & simulation packages.
SCALABLE
Iteratively & rapidly process large number of organic compounds.
FAST
Parameter generation time: <0.01s per compound on a single core node
SSFEP
Single Step Free Energy Perturbation allows free energy calculations 1,000 times faster than with standard FEP. Evaluate thousands of ligand modifications per hour without compromising predictability.
SINGLE STEP FEP
Evaluate Thousands of Ligands per Hour with Single Step FEP!
Rapid calculations by Single Step Free Energy Perturbation minimize lead optimization times in drug discovery.
Free Energy Perturbation (FEP) is the standard approach to calculate relative free energies, but it is often impractical due to its large computational burden. Single Step Free Energy Perturbation (SSFEP) provides an alternative that is 1,000-fold faster than standard FEP, while maintaining comparable accuracy in predicting whether modified ligands bind the target protein better or worse than the parent ligand. After a conditioning step involving the target and ligand, SSFEP uses an automated ligand scanning approach to calculate relative free energies for thousands of ligand transformations per hour.
SSFEP CAN BE USED WITH DIVERSE PROTEIN TARGETS
Single Step FEP methodology can be employed during lead optimization in any structure-based drug discovery project. It ihas been validated across diverse gene family targets including but not limited to traditional targets like Kinases, Proteases, and Nuclear Hormone Receptors and novel epigenetic targets like Methyl Transferases and Bromodomains.
A graphical user interface faciliatates selection of parent ligand R-sites to be modified and provides a library of modifications.
Evaluating a range of modifications at various ligand R-sites reveals which R-sites
are best suited to modification. This information provides focus in downstream
ligand optimization efforts.
BEST FOR
Small functional group changes like -H to -Cl, -OH, -CH3, etc.
QUICK SET-UP
Target conditioning step requires only 30 minutes of set-up time & 3 hours of computer time (on 12 cores + 1 GPU node).
FAST
SSFEP evaluates 1000 ligand modifications per hour.
SILCS-BIOLOGICS
Leading-edge software builds on the patented SILCS technology, using protein-protein interaction and excipient binding predictions to give insights on excipient formulation for biological therapeutics.
SilcsBio offers software and services to unlock the full potential of computer-aided drug design. New developments enable a leading-edge approach to analyze protein-excipient/buffer and protein-protein interactions at an atomic level and give insight on excipient formulation for biologic therapeutics including antibodies and other proteins.
THE PROBLEM
The formulation of biologics has become a major bottleneck in bringing these novel therapies to market. Biologics are formulated to maintain their activity during long-term storage and subsequent administration. Maintaining their 3D conformations and preventing protein aggregation is an important challenge in their development. Experiments to identify the optimal combinations of excipients, buffers, and surfactants are low throughput and require high concentrations of protein – which is limited and costly. Failure to determine the optimal formulation results in decreased product performance; impacting patient treatment and in some cases requiring the costly reengineering of the therapeutic protein.
FragMaps on CNTO607 mAb
variable domain
SILCSBIO INNOVATION
SilcsBio is developing a novel formulation design technology in silico to inform the selection of desired excipient/buffer combinations. With the help of the established SILCS platform, SilcsBio’stechnology 3D maps the protein of interest (FragMap) and its functional group affinity pattern, providing data to enhance stability and prevent aggregation.
BENEFITS
- The SILCS technology allows screening of 100’s of excipients and buffers as well as protein-protein interaction (PPI) within a day, minimizing the need for experimental screening.
- Rational selection of excipient/buffer combinations in silico guided by SilcsBio’s approach will lower costs and timelines in developing novel biologics.
- Improved formulations to better maintain the stability of biologics during storage and delivery.
PPI AND EXCIPIENT BINDING DATA ARE COMBINED TO SCORE VARIOUS EXCIPIENTS
ACCELERATE YOUR RESULTS
WITH SILCSBIO
Connect with us today to learn more about how we can
help your team work faster and more efficiently.
