A Major Step in Molecular Simulation - Key to Designing New Drugs

Researchers at Hospital del Mar Research Institute (IMIM) and Pompeu Fabra University (UPF) have successfully reproduced and reconstructed the complete process of a small molecule binding with its target protein. IMIM and UPF are part of the VPH NoE Network and this project started as part of the VPH NoE's Seed Exemplar Project 4.

This advance enables the calculation of the binding affinity and binding timescale as well as understanding the interactions established by the drug in order to act, thus moving towards safer and more efficient design of new drugs. This groundbreaking project helps show a process that was hitherto invisible and therefore unknown, and opens up a new avenue in the design of new drugs.

The binding process of a drug, usually a small molecule, to its target protein is highly dynamic and depends on interactions at a nanometric scale (billions of times smaller than a metre) and occurs at timescales of nano/micro-seconds (billions of times faster than a second). The capturing of movements of small molecules with a resolution of up to an atom is beyond current technical capabilities. However, using computer techniques, it is possible to represent the molecules at atomic scale and reproduce their movements with high mathematical precision.

Understanding how protein and molecules bind - in which the latter causes a biological response after being recognised by the former (binding) - is vitally important for the design of new drugs. Despite the progress made so far with the technique, no study had provided a complete reconstruction of the protein-ligand binding process. "The method provides not only the binding affinity and the kinetics of the reaction, but also information about the atomic resolution during the process: binding sites, transition states and metastable states are potentially useful for expanding the probability of success when designing drugs. This methodology can be directly applied to other molecular systems and is therefore of general interest in biomedical and pharmaceutical research" explains Gianni de Fabritiis, coordinator of the Computational Biophysics Laboratory of the Biomedical Computer Research Programme (GRIB) run by Hospital del Mar Research Institute (IMIM) and Pompeu Fabra University (UPF).

The researchers are now working to expand the applicability of this methodology and make better use of the computational capabilities as, in cases in which ligands are larger and more flexible and where the proteins involve more complex binding processes, greater computational effort is required.

For further information please see the reference article: "Complete reconstruction of an enzyme-inhibitor binding process by molecular dynamics simulations" IBuch, T Giorgino, G De Fabritiis. www.pnas.org/content/early/2011/05/31/1103547108.abstract

Most Popular Now

Researchers Find Telemedicine may Help R…

Low-value care - medical tests and procedures that provide little to no benefit to patients - contributes to excess medical spending and both direct and cascading harms to patients. A...

AI Revolutionizes Glaucoma Care

Imagine walking into a supermarket, train station, or shopping mall and having your eyes screened for glaucoma within seconds - no appointment needed. With the AI-based Glaucoma Screening (AI-GS) network...

AI may Help Clinicians Personalize Treat…

Individuals with generalized anxiety disorder (GAD), a condition characterized by daily excessive worry lasting at least six months, have a high relapse rate even after receiving treatment. Artificial intelligence (AI)...

Accelerating NHS Digital Maturity: Paper…

Digitised clinical noting at South Tees Hospitals NHS Foundation Trust is creating efficiencies for busy doctors and nurses. The trust’s CCIO Dr Andrew Adair, deputy CCIO Dr John Greenaway, and...

Mobile App Tracking Blood Pressure Helps…

The AHOMKA platform, an innovative mobile app for patient-to-provider communication that developed through a collaboration between the School of Engineering and leading medical institutions in Ghana, has yielded positive results...

AI can Open Up Beds in the ICU

At the height of the COVID-19 pandemic, hospitals frequently ran short of beds in intensive care units. But even earlier, ICUs faced challenges in keeping beds available. With an aging...

Can AI Help Detect Cognitive Impairment?

Mild cognitive impairment (MCI) can be an early indicator of Alzheimer's disease or dementia, so identifying those with cognitive issues early could lead to interventions and better outcomes. But diagnosing...

Customized Smartphone App Shows Promise …

A growing body of research indicates that older adults in assisted living facilities can delay or even prevent cognitive decline through interventions that combine multiple activities, such as improving diet...

New Study Shows Promise for Gamified mHe…

A new study published in Multiple Sclerosis and Related Disorders highlights the potential of More Stamina, a gamified mobile health (mHealth) app designed to help people with Multiple Sclerosis (MS)...

AI Model Predicting Two-Year Risk of Com…

AFib (short for atrial fibrillation), a common heart rhythm disorder in adults, can have disastrous consequences including life-threatening blood clots and stroke if left undetected or untreated. A new study...

Patients' Affinity for AI Messages …

In a Duke Health-led survey, patients who were shown messages written either by artificial intelligence (AI) or human clinicians indicated a preference for responses drafted by AI over a human...

New Research Explores How AI can Build T…

In today’s economy, many workers have transitioned from manual labor toward knowledge work, a move driven primarily by technological advances, and workers in this domain face challenges around managing non-routine...