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Synopsis of the 15th KIAS conference on ProteinStructure and FunctionSeptember 17th - 19th, 2015

글 _ Andrew V. Brooks

A fortnight before its 19th birthday, KIAS, in collaboration with the Center for In Silico Protein Science, had the privilege of hosting its 15th Conference on Protein Structure and Function.

With only three days to get through twenty-seven lectures, forty-one posters, and six coffee breaks, Professor Jooyoung Lee of the host institution and Director of the Center for In Silico Protein Science gave an expedient and heartfelt welcome, immediately yielding to the first speaker. I am happy to announce that ten of the invited twenty-four speakers were also presenting with us here for the first time.

During the first day, Professor Sihyun Ham of Sookmyung Women’s University and Professor Takayuki Uchihashi of Kanazawa University each excitedly gave detailed accounts of their recent advances in biomolecular visualization. While Uchihashi observed actual atom movements by even higher-speed atomic force microscopy (HS-AFM), Ham’s research

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was demonstrated through the usage of realistic video simulations, achievable by a novel application of fluctuating thermodynamic calculations capable of keeping up with the wavering nuances of biological systems.

This symmetrical focus on both the empirically observed and the painstakingly calculated provides some insight into the future of biophysics. While there is a struggle for refinement and funding on both ends, the health of the field hinges on what a combined usage of modeling and experimentation can elucidate about reality.

Over half of the lectures given at this conference, and about half of the posters presented, incorporated simulation or modeling of macromolecular structure and function in some fashion: either employing their predictive capabilities as supplement to or reference for experimental data, or engaging in the optimization and science of both simulations and data. The time it takes to run a simulation is an important resource, after all.

An example of this is Seoul National University’s Dr. Seokmin Shin and his research on improving sampling efficiency in simulations of complex systems. This was sought through the combined optimization of two extant replica exchange methods (REM) named tq-REM. Professor Jooyoung Lee himself gave the closing lecture of the whole conference, citing the work his whole lab has been developing over the last year: a continuation of their previous work done on the critical assessment of techniques for protein structure prediction (CASP). This talk, in particular, pertaining to a combinatorial three-tiered optimization of their conformational space annealing methodology so as to incorporate multiple structure-structure alignment, 3D modeling, and side-chain reorganization into their model generation and assessment efforts.

In the ongoing spirit of this integration, Drs. Melissa and Matthew Hall of the Walter and Eliza Hall Institute of Medical Research presented research where simulations were employed in studying the enigmatic transmission of information through membranes. It was during Matthew’s presentation on the third and final day of the conference when he acknowledged that “modeling and simulations play an increasing role for interpreting experimental data,” and that “as the accuracy of reproducing the experimental structures [of proteins] increases, reliable predictions can be made.”

In addition to the Halls, we had another team of married speakers each present their research done at the National Institutes of Health (NIH). Drs. Frank Pickard and Florentina Tofoleanu had so far spent the majority of their married life on airplanes, but were still eager

Professor Sihyun Ham of Sookmyung Women’s University, fourth lecture of the first day

Professor Jooyoung Lee giving the last lecture of the conference.

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to discuss the collaboration between experimental and computational models enabled by the expanding capabilities of the CHARMM simulation package.

Needless to say, there is pressure to refine this type of analysis. The needs of the industry have sparked a maturation within the field of modeling itself. That being: an incorporation of , long-range and large scale quantitative contexts so as to predict the function and structure of proteins and their interactions in increasingly more accurate representations of their natural and neighboring environments.

Long time veteran of this conference, and no stranger to KIAS, was Dr. Bernard R. Brooks from the NIH who presented a lecture on the recent advances in explicit state constant pH modeling methods to be applied toward the improvement of multi-scale modeling in structural biology and biophysics

Also in this vein, Dr. Daisuke Kihara from Purdue University spoke of his group’s novel coarse-grained scoring functions which take into account the native-likeness of a protein’s local structure environment, including neighboring residues. Additionally, Dr. Matthias Heyden from the Max-Planck-Institut für Kohlenforschung and Dr. Eri Chatani from Kobe University, as well as five other speakers and nine posters that I wish I could mention with

equal depth, each presented research that concerned a protein’s solvating environment. In the case of these two speakers, water molecule system dynamics were employed in some fashion in order to elucidate the behaviour of proteins in natural, crowded, and salty environments.

What stood out to me most of all during the conference was a growing realization that protein modeling techniques in particular undergo a kind of evolution, coincidentally not unlike the symbiogenesis

of organelles. Every year, a scattering of methods and terms, both old and new, are remixed, enjoined, and put to the test. A test demanding their programmers read between the lines of code. Whether they turn out to be momentary attempts or enduring practices is a function of their performance, and our creative ability to analyze the results.

In the spirit of this relentless evolutionary pressure exerted on the codes and methodologies of computational biophysicists everywhere, Dr. Charles L. Brooks III of the University of Michigan had this piece of advice for all the students in the audience during his lecture on multi-scale modeling: “Take your models and put them where they don’t belong. Break them, because that’s where you learn things.” In other words, in order to truly understand what your code is doing when it’s behaving, you must first delimit its unknown functionalities;

Biophysicists in their natural, crowded, environment, in various states of caffeination.

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its unseen interferences; its unintentional entanglements. Only then can your modeling adapt and grow.

But even if life as epistemological concept seems often relegated to the periphery of the field, as if we are all well aware its mysteries, sometimes we stumble upon new ground. Dr. Juyong Lee, also representing the NIH, indeed may have done precisely this, and so presented his research on the construction of a global weighted network of all protein binding sites in tandem with community detection. They found that the largest communities, determined by all-to-all similarities, consisted mainly of metal binding sites -- in particular Zn2+ sites -- which may also potentially be the oldest. Their findings correlated curiously with Zinc-World theories of abiogenesis, and raise questions about the nature of life everywhere...

...At least in the cosmological sense. In the cases for new life, Dr. Nobuyasa Koga of The National Institute of Natural Sciences in Japan presented his research on designing protein models from scratch, namely, idealized protein structures whose artificiality can be optimized completely for folding or other such qualities. He argued that the long evolutionary histories of naturally occurring proteins obscure and limit our capacity to understand protein behaviour, in toto. Guided by a determined set of rules which dictate protein energy landscapes, they found that their synthesized designs adopt structures in solution nearly identical to their computational models. He finished with a quote from Richard Feynman, “What I can’t create I don’t understand.”

At the end of the first day, the poster session opened and invited speakers were petitioned to select their top five choices by rank. I would like to take a moment here to recognize the winners:

Yoon-Mo Yang of Korea Institute of Ocean Science and TechnologyStructural Analysis of Apo-form and Holo-form of Gram-Positive Fur

Minkyung Baek of Seoul National UniversityDevelopment of Hybrid Scoring Function for Accurate Protein Ligand Docking Inhwan Lee of Yonsei UniversityCrystal Structure of Syndesmos and Its Interaction with Syndecan-4 Proteoglycan

Yoon-Mo Yang talks with Dr. Matthew Hall (background) and Dr. Kunihiro Kuwajima (foreground)

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Sunhee Cho of Sookmyung Women’s UniversityComputational Study on the Fluorescent Probe for the Detection of the Aβ Oligomers

Sanghun Yeou of Pohang University of Science and TechnologyReal-time submillisecond observation of freely diffusing molecules by liposome tethering single molecule FRET analysis.

Cheolhee Kim of Pohang University of Science and TechnologyDynamic release of bending energy in short double-stranded DNA by two types of deformation: Single-molecule FRET study

All in all, the three days went by very quickly, even with all of the excursions and dinners taken into account. Saying nothing of the speakers’ own eating habits when back in their labs, there were no shortages of feasts to go around where we could relax and learn a little bit more from and about each other. I can think of no better way to honor the diversity of backgrounds and cultures we all come from than sharing tales of our homes over a meal.

In fact, we at KIAS had the privilege of being culinary guinea pigs for a few days leading up to the conference, testing on ourselves with reckless abandon all the different menu options offered at some of the most popular places in KIAS’s orbit. Each meal a worthy sacrifice in honor of our guests. Our fascination with food even had speaker Dr. Changbong Hyeon of KIAS comparing interchromosomal contact probability to different kinds and gauges of pasta as an analogy to the crowding of polymers of different lengths when confined in small volumes.

But it will be at least another year before we again leave our labs and confine ourselves in small volume at KIAS’s lecture hall for the 16th Annual Conference on Protein Structure and Function.

I’d like to take this last moment to give one last round of thanks to our speakers, our poster presenters, the organizers of KIAS -- in particular Ms. Mikyung Nam who was in charge of all of the administrative efforts that make meetings like this possible; may they never go unnoticed! -- as well as the caterers who fueled us with the much needed caffeine; and one last special thanks to the volunteer timekeepers, for without their help we people of science may very well just go on talking forever.

(Hope to) See you next year!