Activity
-
We just shared our latest Mayo Clinic Business Development newsletter, and there’s a lot of happenings to be excited about at Mayo Clinic and within…
We just shared our latest Mayo Clinic Business Development newsletter, and there’s a lot of happenings to be excited about at Mayo Clinic and within…
Liked by Murali Aravamudan
-
Did you know that two of the world’s most widely used weight-loss medicines can lead to significantly different real-world outcomes? This week’s new…
Did you know that two of the world’s most widely used weight-loss medicines can lead to significantly different real-world outcomes? This week’s new…
Liked by Murali Aravamudan
-
Metabolism is the quiet force that shapes every year of our lives. It dictates how we gain weight, how we lose it, how we age, how we feel, and how…
Metabolism is the quiet force that shapes every year of our lives. It dictates how we gain weight, how we lose it, how we age, how we feel, and how…
Liked by Murali Aravamudan
Publications
-
Global connectivity of hub residues in Oncoprotein structures encodes genetic factors dictating personalized drug response to targeted Cancer therapy
Nature Scientific Reports
The efficacy and mechanisms of therapeutic action are largely described by atomic bonds and interactions local to drug binding sites. Here we introduce global connectivity analysis as a high-throughput computational assay of therapeutic action – inspired by the Google page rank algorithm that unearths most “globally connected” websites from the information-dense world wide web (WWW). We execute short timescale (30 ps) molecular dynamics simulations with high sampling frequency (0.01 ps), to…
The efficacy and mechanisms of therapeutic action are largely described by atomic bonds and interactions local to drug binding sites. Here we introduce global connectivity analysis as a high-throughput computational assay of therapeutic action – inspired by the Google page rank algorithm that unearths most “globally connected” websites from the information-dense world wide web (WWW). We execute short timescale (30 ps) molecular dynamics simulations with high sampling frequency (0.01 ps), to identify amino acid residue hubs whose global connectivity dynamics are characteristic of the ligand or mutation associated with the target protein. We find that unexpected allosteric hubs – up to 20Å from the ATP binding site, but within 5Å of the phosphorylation site – encode the Gibbs free energy of inhibition (ΔGinhibition) for select protein kinase-targeted cancer therapeutics. We further find that clinically relevant somatic cancer mutations implicated in both drug resistance and personalized drug sensitivity can be predicted in a high-throughput fashion. Our results establish global connectivity analysis as a potent assay of protein functional modulation. This sets the stage for unearthing disease-causal exome mutations and motivates forecast of clinical drug response on a patient-by-patient basis. We suggest incorporation of structure-guided genetic inference assays into pharmaceutical and healthcare Oncology workflows.
Other authorsSee publication
More activity by Murali
-
𝗟𝗶𝗳𝗲 𝗰𝗼𝗺𝗲𝘀 𝗳𝘂𝗹𝗹 𝗰𝗶𝗿𝗰𝗹𝗲! I am a proud "railways brat" 🚂 - born & raised in a railway family and educated in railway schools…
𝗟𝗶𝗳𝗲 𝗰𝗼𝗺𝗲𝘀 𝗳𝘂𝗹𝗹 𝗰𝗶𝗿𝗰𝗹𝗲! I am a proud "railways brat" 🚂 - born & raised in a railway family and educated in railway schools…
Liked by Murali Aravamudan
-
I’m proud to share that Boston Scientific enrolled the first patients in the OPTIMIZE randomized controlled trial. This trial uses the novel Cortex…
I’m proud to share that Boston Scientific enrolled the first patients in the OPTIMIZE randomized controlled trial. This trial uses the novel Cortex…
Liked by Murali Aravamudan
-
AHA Day 1: Come see transparency in action. At Booth 4719, we're inviting the cardiology community to test our ECG-AI technology with their own data.…
AHA Day 1: Come see transparency in action. At Booth 4719, we're inviting the cardiology community to test our ECG-AI technology with their own data.…
Liked by Murali Aravamudan
-
When I saw this video from Arrived-AI (the soul of which is Barghavi G), it evoked a mental state in a biological agent (me) that is most likely…
When I saw this video from Arrived-AI (the soul of which is Barghavi G), it evoked a mental state in a biological agent (me) that is most likely…
Liked by Murali Aravamudan
-
Today is a special day – the type that reminds you why you chose a career in making medicines that change people’s lives. At #ESMO25, Parabilis…
Today is a special day – the type that reminds you why you chose a career in making medicines that change people’s lives. At #ESMO25, Parabilis…
Liked by Murali Aravamudan
-
Congratulations to Mike Mussallem, former chairman and CEO of Edwards Lifesciences, on being named the 2025 Lifetime Achievement Award recipient at…
Congratulations to Mike Mussallem, former chairman and CEO of Edwards Lifesciences, on being named the 2025 Lifetime Achievement Award recipient at…
Liked by Murali Aravamudan
-
Cedars-Sinai has received a $26 million award from the federal Patient-Centered Outcomes Research Institute to study treatments for bicuspid aortic…
Cedars-Sinai has received a $26 million award from the federal Patient-Centered Outcomes Research Institute to study treatments for bicuspid aortic…
Liked by Murali Aravamudan
-
Great start to our Mayo Clinic course on AI in Cardiology here in Napa. Tonight’s session - An evening with AI companies, kicked off the course with…
Great start to our Mayo Clinic course on AI in Cardiology here in Napa. Tonight’s session - An evening with AI companies, kicked off the course with…
Liked by Murali Aravamudan
-
Throughout my career, I have been incredibly fortunate to cross paths with mentors whose wisdom and encouragement changed my trajectory. Mentors like…
Throughout my career, I have been incredibly fortunate to cross paths with mentors whose wisdom and encouragement changed my trajectory. Mentors like…
Liked by Murali Aravamudan
-
I'm very excited to be participating in The Agentic AI Innovation Summit. This is a great opportunity to join the conversation on shaping the future…
I'm very excited to be participating in The Agentic AI Innovation Summit. This is a great opportunity to join the conversation on shaping the future…
Liked by Murali Aravamudan
-
I was proud to share the stage with Ken Stein, senior vice president and global chief medical officer at Boston Scientific, during our recent…
I was proud to share the stage with Ken Stein, senior vice president and global chief medical officer at Boston Scientific, during our recent…
Liked by Murali Aravamudan
Other similar profiles
Explore top content on LinkedIn
Find curated posts and insights for relevant topics all in one place.
View top content